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Due to the extensive use of plastic products and unreasonable disposal, nanoplastics contamination has become one of the important environmental problems that mankind must face. The composition and structure of porous media can determine the complexity and diversity of the transport behavior of nanoplastics. In this study, the influence of diatomite (DIA) on the nanoplastics transport in porous media is investigated by column experiments combined with XDLVO interaction energy and transport model. Results suggest that the recovery rates of unmodified polystyrene nanoparticles (PSNPs) and carboxyl-modified polystyrene nanoparticles (PSNPs-COOH) in the porous media containing DIA decreases compared with that in the pure quartz sand (QS), and the BTCs showed a "blocking" pattern. The presence of DIA inhibits the transport of both PSNPs and PSNPs-COOH, but the inhibition is not significant. This may be because the presence of DIA provides more favorable deposition sites for PSNPs and PSNPs-COOH to some extent. However, since DIA itself carries a certain negative charge, this can only play a role in compressing the double electric layer for PSNPs and PSNPs-COOH with the same negative charge, and cannot destabilize them. The migration capacity of PSNPs and PSNPs-COOH is strongest in the DIA-QS porous media at pH = 7, and is weak at pH = 9 and pH = 5. The inhibition of migration at pH = 9 can be attributed to the dissolution of the DIA surface under alkaline conditions and the formation of pore and defect structures, which provide more deposition sites for PSNPs and PSNPs-COOH. The presence of humic acid (HA) leads to an increase in the mobility of PSNPs and PSNPs-COOH, and the mobility is enhanced with HA concentration. The mobility of PSNPs and PSNPs-COOH in DIA-QS decreases with ionic valence and ionic strength, and PSNPs-COOH is more significantly inhibited compared to PSNPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children., Methods: Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed., Results: Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26-100%). The sensitivity of BDG was 57.58% (95% CI: 39.22-74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts., Conclusions: The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management., (© 2024. The Author(s).)

Introduction: Paxlovid (nirmatrelvir/ritonavir) has received endorsement from several guidelines for treating COVID-19 in adults, but its use in children is still uncertain., Objectives: This study aimed to evaluate the safety and effectiveness of paxlovid in pediatric patients in the pediatric intensive care unit (PICU)., Methods: A retrospective analysis was performed on children with COVID-19. The children who received paxlovid comprised the paxlovid group; otherwise, they were referred to as the control group., Results: A total of 31 children were enrolled, with 12 and 19 participants assigned to the paxlovid and control groups, respectively. Approximately 35% had received vaccination against the novel coronavirus. The control group exhibited a significantly lower mean age in comparison to the paxlovid group (p < 0.001). However, no significant differences were observed between the groups in terms of other baseline data and biochemical indexes at admission. However, on the fifth day of drug administration, the paxlovid group exhibited a statistically significant decrease in temperature compared to the control group (p < 0.05). Additionally, the paxlovid group exhibited a significantly shorter conversion time to negativity for novel coronary genes in the respiratory tract (9.5 days) compared to the control group (16 days, p < 0.05). The administration of paxlovid did not result in any observed adverse reactions. Merely two patients exhibited a transient elevation in liver enzyme levels., Conclusion: The application of paxlovid in critically ill pediatric patients with COVID-19 can effectively control symptoms and promote virus clearance, demonstrating efficacy and a relatively low-risk profile., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

With the application of engineered nanomaterials and antibiotics in the fields of medicine, aerospace, new energy and agriculture, the associated contamination is detected widely in soil-groundwater systems. It is of great scientific and practical significance to deeply explore the environmental interface process between nanoparticles and antibiotics for the scientific assessment of environmental fate and ecological environmental risks, as well as the development of new composite pollution control technologies. In this study, the co-transport behaviors of positively charged titanium dioxide nanoparticles (TiO 2 -NPs) and negatively charged levofloxacin (LEV) in quartz sand (QS) are investigated in this study. The results show that TiO 2 -NPs hardly flow out when transported alone in the column because of its positive charge, which creates a strong attraction with the negatively charged quartz sand on the surface. When TiO 2 -NPs co-migrate with LEV in porous media, the presence of LEV promotes the transport of TiO 2 -NPs, while the presence of TiO 2 -NPs inhibits LEV transport. Non-XDLVO interactions based on molecular dynamics (MD) simulations can help explain the observed promotion and inhibition phenomena as well as the correlation between TiO 2 -NPs and LEV. The results indicate that TiO 2 -LEV complexes or aggregates can be formed during the co-transportation process of TiO 2 -NPs and LEV in porous media. As flow velocity increases from 0.204 cm min -1 to 1.630 cm min -1 , both the transport capacities of TiO 2 -NPs and LEV are enhanced significantly. Under the condition of high citric acid (CA) concentration (15 mmol L -1 ), the transport capacity of TiO 2 -NPs is slightly inhibited, while the transport capacity of LEV is enhanced. This study provides new insights into the transport of nanometallic oxides and antibiotics in porous media, which suggests that non-XDLVO interactions should be considered together when assessing the environmental risks and fate of nanometallic oxides and antibiotics in soil-groundwater systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence., Methods: Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level ( P < 5×10 -8 ). The sensitivity analysis was conducted to assess the reliability of the MR estimates., Results: Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI ( OR = 1.29, P = 0.003), childhood obesity ( OR = 1.07, P = 0.034), adult BMI ( OR = 1.38, P < 0.001), adult waist circumference ( OR = 1.01, P = 0.028), and adult visceral adiposity ( OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results., Conclusion: The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cheng, Li, Tong, Liu, Zhang, Ma and Lu.)

Tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) is increasing and has emerged as a global public health issue. However, the mechanism of tigecycline resistance remains unclear. The objective of this study was to investigate the potential role of efflux pump system in tigecycline resistance. 29 tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) strains were collected and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The ramR, acrR, rpsJ, tet(A), and tet(X) were amplified by polymerase chain reaction (PCR). The mRNA expression of different efflux pump genes and regulator genes were analyzed by real-time PCR. Additionally, KP14 was selected for genome sequencing. KP14 genes without acrB, oqxB, and TetA were modified using suicide plasmids and MIC of tigecycline of KP14 with target genes knocked out was investigated. It was found that MIC of tigecycline of 20 out of the 29 TNSKP strains decreased by over four folds once combined with phenyl-arginine-β-naphthylamide dihydrochloride (PaβN). Most strains exhibited upregulation of AcrAB and oqxAB efflux pumps. The strains with acrB, oqxB, and tetA genes knocked out were constructed, wherein the MIC of tigecycline of KP14∆acrB and KP14∆tetA was observed to be 2 µg/mL (decreased by 16 folds), the MIC of tigecycline of KP14ΔacrBΔTetA was 0.25 µg/mL (decreased by 128 folds), but the MIC of tigecycline of KP14∆oqxB remained unchanged at 32 µg/mL. The majority of TNSKP strains demonstrated increased expression of AcrAB-TolC and oqxAB, while certain strains showed mutations in other genes associated with tigecycline resistance. In KP14, both overexpression of AcrAB-TolC and tet(A) gene mutation contributed to the mechanism of tigecycline resistance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To investigate the clinical characteristics and molecular epidemiology of CRKP infection in neonatal patients in a children's hospital in China from 2017 to 2021., Methods: Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. The clinical data were collected from medical records. Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were investigated by antimicrobial susceptibility testing, carbapenemase genes and multilocus sequence typing., Results: Six kinds of resistant genes and 23 STs were detected. Bla NDM-1 (n=83, 55.3%) was the predominant carbapenemase gene, followed by bla KPC-2 (n=45, 30.0%), bla NDM-5 (n=7, 4.7%), bla IMP-38 (n=6, 4.0%). Bla NDM-1 was predominant in 2017 and 2018, whereas bla KPC-2 increased in 2019 and became the predominant gene from 2020 to 2021. ST11 accounted for most infections (n=35, 23.3%), followed by ST278 (n=23, 15.3%), ST17 (n=17, 11. 3%) and ST2735 (n=16, 10.7%). ST278 and ST17 were predominant in 2017 and 2018, whereas ST11 increased in 2019 and became the predominant sequence type from 2020 to 2021. Compared with bla NDM-1 , the CRKP strains producing bla KPC-2 were characterized by high resistance to gentamicin, amikacin and levofloxacin and the change trend of drug resistance rate before and after COVID-19 was consistent with that of bla NDM-1 and bla KPC-2 ., Conclusions: The main sequence type of CRKP infection changed dynamically from ST278-NDM-1 to ST11-KPC-2 during the years 2017-2021 in the newborns. Antibiotic exposure and the prevalence of COVID-19 since 2020 may have led to changes in hospital population and lead to the changes., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses immense threats to the health of infected patients worldwide, especially children. This study reports the infection caused by CRKP in a paediatric intensive care unit (PICU) child and its drug-resistant mutation during the treatment. Twelve Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains were isolated from the child. Broth microdilution method, plasmid transformation assay, and whole genome sequencing (WGS) were performed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural features of CRKPs. The results showed that 12 strains were highly resistant to most available antimicrobial agents. Among them, K. pneumoniae FD11 and K. pneumoniae FD12 were resistant to ceftazidime-avibactam (CZA, MIC >64 mg/L) and restored the carbapenem susceptibility (Imipenem, MIC =0.25 mg/L; Meropenem, MIC =2 mg/L). The patient improved after treatment with CZA in combination with aztreonam. Plasmid transformation assay demonstrated that the bla KPC-33 -positive transformant increased MICs of CZA by at least 33-fold and 8-fold compared with the recipient Escherichia coli DH5α and bla KPC-2 -positive transformants. WGS analysis revealed that all strains belonged to the ST11-KL64 type and showed highly homologous (3-26 single nucleotide polymorphisms [SNPs]). A single base mutation (G532T) of bla KPC-2 resulted in a tyrosine to aspartic acid substitution at Ambler amino acid position 179 (D179Y), which conferred CZA resistance in K. pneumoniae. This is the first report of a drug-resistant mutation evolving into bla KPC-33 during the treatment of bla KPC-2 -positive CRKP in paediatric-infected patients. It advises clinicians that routine sequential antimicrobial susceptibility testing and KPC genotyping are critical during CZA therapy in children infected with CRKP., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objective: To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China., Methods: A prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study., Results: Out of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15-0.84; P  = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17-1.61; P  < .001). Conversely, early rehabilitation intervention was negatively associated with the risk of PMV death (OR = 0.45; 95% CI: 0.22-0.93; P  = .032). Furthermore, the tracheotomy timing emerged as an independent predictor of failure to wean from PMV, with an OR of 1.08, (95% CI: 1.01-1.16; P   =  .030)., Conclusions: The study revealed a 5.3% incidence of PMV in children requiring mechanical ventilation in China. The use of vasoactive agents and a higher PELOD-2 score at PMV diagnosis were significantly associated with an increased risk of PMV death, whereas early rehabilitation intervention was identified as crucial for improving patient outcomes. The timing of tracheostomy was identified as a high-risk factor for failure to wean from mechanical ventilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Cai, Ming, Huang, Liu, Ren, Qu, Gao, Cheng, Zhang, Yang, Xu, Miao, Liu, Liu, Lu and Chen.)

Background: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making., Methods: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated., Results: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii., Conclusions: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST., (© 2024. The Author(s).)

In this study, we devised a diagnostic platform harnessing a combination of recombinase polymerase amplification (RPA) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system. Notably, this platform obviates the need for intricate equipment and finds utility in diverse settings. Two result display methods were incorporated in this investigation: the RPA-Cas12a-fluorescence method and the RPA-Cas12a-LFS (lateral flow strip). Upon validation, both display platforms exhibited no instances of cross-reactivity, with seven additional types of fungal pathogens responsible for respiratory infections. The established detection limit was ascertained to be as low as 10 2 copies/µL. In comparison to fluorescence quantitative PCR, the platform demonstrated a sensitivity of 96.7%, a specificity of 100%, and a consistency rate of 98.0%.This platform provides expeditious, precise, and on-site detection capabilities, thereby rendering it a pivotal diagnostic instrument amenable for deployment in primary healthcare facilities and point-of-care settings., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Myeloid-derived suppressor cells (MDSCs) expand during sepsis and contribute to the development of persistent inflammation-immunosuppression-catabolism syndrome. However, the underlying mechanism remains unclear. Exploring the mechanisms of MDSCs generation may provide therapeutic targets for improving immune status in sepsis. Here, a sepsis mouse model is established by cecal ligation and perforation. Bone marrow cells at different sepsis time points are harvested to detect the proportion of MDSCs and search for differentially expressed genes by RNA-sequence. In lethal models of sepsis, polymorphonuclear-MDSCs (PMN-MDSCs) decrease in early but increase and become activated in late sepsis, which is contrary to the expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1). In vivo , Malat1 inhibitor significantly increases the mortality in mice with late sepsis. And in vitro , Malat1 down-regulation increases the proportion of PMN-MDSCs and enhanced its immunosuppressive ability. Mechanistically, Malat1 limits the differentiation of PMN-MDSCs by accelerating the degradation of phosphorylated STAT3. Furthermore, Stattic, an inhibitor of STAT3 phosphorylation, improves the survival of septic mice by inhibiting PMN-MDSCs. Overall, the study identifies a novel insight into the mechanism of sepsis-induced MDSCs and provides more evidence for targeting MDSCs in the treatment of sepsis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Because of the intricate topological structure and connection of the human brain, extracting deep spatial features from electroencephalograph (EEG) signals is a challenging and time-consuming task. The extraction of topological spatial information plays a crucial role in EEG classification, and the architecture of the spatial convolution greatly affects the performance and complexity of convolutional neural network (CNN) based EEG classification models. In this study, a progressive convolution CNN architecture named EEGProgress is proposed, aiming to efficiently extract the topological spatial information of EEG signals from multi-scale levels (electrode, brain region, hemisphere, global) with superior speed. To achieve this, the raw EEG data is permuted using the empirical topological permutation rule, integrating the EEG data with numerous topological properties. Subsequently, the spatial features are extracted by a progressive feature extractor including prior, electrode, region, and hemisphere convolution blocks, progressively extracting the deep spatial features with reduced parameters and speed. Finally, the comparison and ablation experiments under both cross-subject and within-subject scenarios are conducted on a public dataset to verify the performance of the proposed EEGProgress and the effectiveness of the topological permutation. The results demonstrate the superior feature extraction ability of the proposed EEGProgress, with an average increase of 4.02% compared to other CNN-based EEG classification models under both cross-subject and within-subject scenarios. Furthermore, with the obtained average testing time, FLOPs, and parameters, the proposed EEGProgress outperforms other comparison models in terms of model complexity., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tumor-associated macrophages (TAMs) are critical in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Major vault protein (MVP) mediates multidrug resistance, cell growth and development, and viral immunity. However, the relationship between MVP and TAMs polarization has not been clarified in HCC. We found that MVP significantly increased M2-TAMs infiltration levels in tumor tissues of HCC patients. MVP promoted HCC proliferation, metastasis, and invasion by regulating M2 polarization in vivo and in vitro . Mechanistically, MVP associated with signal transducer and activator of transcription 6 (STAT6) and enhanced STAT6 phosphorylation. STAT6 translocated from the cytosol to the nucleus and regulated M2 macrophage-associated gene transcription. These findings suggest that MVP modulates the macrophage M2 transcriptional program, revealing its potential role in the TAMs of TME., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Zhu, Ma, Luo, Nie, Cai, Wang, Wang, Ren, Yan, Xu, Zhou, Zhang, Lu, Lu, Zhu and Liu.)

Background: Acute kidney injury (AKI) is a common and serious organ dysfunction in critically ill children. Early identification and prediction of AKI are of great significance. However, current AKI criteria are insufficiently sensitive and specific, and AKI heterogeneity limits the clinical value of AKI biomarkers. This study aimed to establish and validate an explainable prediction model based on the machine learning (ML) approach for AKI, and assess its prognostic implications in children admitted to the pediatric intensive care unit (PICU)., Methods: This multicenter prospective study in China was conducted on critically ill children for the derivation and validation of the prediction model. The derivation cohort, consisting of 957 children admitted to four independent PICUs from September 2020 to January 2021, was separated for training and internal validation, and an external data set of 866 children admitted from February 2021 to February 2022 was employed for external validation. AKI was defined based on serum creatinine and urine output using the Kidney Disease: Improving Global Outcome (KDIGO) criteria. With 33 medical characteristics easily obtained or evaluated during the first 24 h after PICU admission, 11 ML algorithms were used to construct prediction models. Several evaluation indexes, including the area under the receiver-operating-characteristic curve (AUC), were used to compare the predictive performance. The SHapley Additive exPlanation method was used to rank the feature importance and explain the final model. A probability threshold for the final model was identified for AKI prediction and subgrouping. Clinical outcomes were evaluated in various subgroups determined by a combination of the final model and KDIGO criteria., Findings: The random forest (RF) model performed best in discriminative ability among the 11 ML models. After reducing features according to feature importance rank, an explainable final RF model was established with 8 features. The final model could accurately predict AKI in both internal (AUC = 0.929) and external (AUC = 0.910) validations, and has been translated into a convenient tool to facilitate its utility in clinical settings. Critically ill children with a probability exceeding or equal to the threshold in the final model had a higher risk of death and multiple organ dysfunctions, regardless of whether they met the KDIGO criteria for AKI., Interpretation: Our explainable ML model was not only successfully developed to accurately predict AKI but was also highly relevant to adverse outcomes in individual children at an early stage of PICU admission, and it mitigated the concern of the "black-box" issue with an undirect interpretation of the ML technique., Funding: The National Natural Science Foundation of China, Jiangsu Province Science and Technology Support Program, Key talent of women's and children's health of Jiangsu Province, and Postgraduate Research & Practice Innovation Program of Jiangsu Province., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

This technical paper investigates the cluster synchronization of finite-field networks (FFNs) based on the algebraic state space representation. By resorting to the semi-tensor product of matrices, the cluster synchronization of an FFN can be completely converted into the set stability of state trajectory. Then, a necessary and sufficient condition for the cluster synchronization of FFNs is obtained based on the invariant subset and one-step transition matrix. In particular, the obtained results are applicable to check the leader-follower synchronization and group consensus of FFNs. Finally, a numerical example is given to illustrate the feasibility of the obtained results.

Cytokine storms are crucial in the development of various inflammatory diseases, including sepsis and autoimmune disorders. The immunosuppressive cytokine INTERLEUKIN (IL)-37 consists of five isoforms (IL-37a-e). We identified IL-37a as a nuclear cytokine for the first time. Compared to IL-37b, IL-37a demonstrated greater efficacy in protecting against Toll-like receptor-induced cytokine hypersecretion and lethal endotoxic shock. The full-length (FL) form of IL-37a and the N-terminal fragment, which is processed by elastase, could translocate into cell nuclei through a distinctive nuclear localization sequence (NLS)/importin nuclear transport pathway. These forms exerted their regulatory effects independent of the IL-1R8 receptor by transcriptionally upregulating the nuclear receptor peroxisome proliferator-activated receptor (PPARγ). This process involved the recruitment of the H3K4 methyltransferase complex WDR5/MLL4/C/EBPβ and H3K4me1/2 to the enhancer/promoter of Pparg. The receptor-independent regulatory pathway of the nuclear IL-37a-PPARγ axis and receptor-dependent signaling by secreted IL-37a maintain homeostasis and are potential therapeutic targets for various inflammatory diseases, including sepsis., (© 2023. The Author(s), under exclusive licence to CSI and USTC.)

Aims: Status epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics., Methods: Ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group (N = 13) with the good outcome group (N = 15) of children with SE. Differentially expressed metabolites were identified using Mann-Whitney U test corrected by Benjamini-Hochberg and partial least squares discriminant analysis (PLS-DA)., Results: The PLS-DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS-DA with R 2 Y = 0.992 and Q 2  = 0.798). A total of 49 prognosis-related metabolites were identified. Of these metabolites, 20 including glutamyl-glutamine, 3-iodothyronamine, and L-fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl-glutamine and 3-iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis., Conclusions: This study highlighted the prognosis-related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl-glutamine and 3-iodothyronamine with high predictive value was established., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

In this study, a combination of column experiments, interface chemistry theory and transport model with two-site kinetics was used to systematically investigate the effect of pH on the transport of polystyrene nanoparticles (PSNPs) in porous media. The porous media containing quartz sand (QS) and three kinds of clay minerals (CMs)-kaolinite (KL), illite (IL) and montmorillonite (MT), was used in column experiments to simulate the porous media in the soil-groundwater systems. Experimental results showed that the inhibitory effect of CMs on the transport of PSNPs is weakened as pH increases. The two-dimensional (2D) surface of the DLVO interaction energy (2D-pH-DLVO) was built to calculate the interactions between PSNPs and CMs under different conditions of pH. Results suggested the inflection point of PSNP-QS, PSNP-KL, PSNP-IL and PSNP-MT are 2.42, 3.30, 2.84 and 3.69, respectively. Most importantly, there was a significant correlation between the two-site kinetic parameters related to PSNPs transport and the DLVO energy barrier (DB). The contributions of the interactions of PSNPs-PSNPs and PSNPs-minerals were determined for PSNPs transport in porous media. The critical values of pH related to the migration ability of PSNPs in porous media could be determined by a combination of column experiments, 2D-pH-DLVO and PSNPs transport model. The critical values of pH were 2.95-3.01, 3.22-3.51, 2.98-3.02, 3.31-3.33 for the migration ability of PSNPs in QS, QS + KL, QS + IL and QS + MT porous media, respectively. The stronger migration ability of PSNPs under high pH conditions is attributed to the enhanced deprotonation of the media surface and increased negative surface charge, which increases the electrostatic repulsion between PSNPs and porous media (QS, CMs). Moreover, the agglomeration of PSNPs usually is weaker and the average particle size of agglomerates is smaller under the condition of high pH, thus leading to the stronger migration ability of PSNPs under high pH conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples., Methods: A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients' lung BALF microbiomes were explored using the mNGS data., Results: Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%)., Conclusions: mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs., Competing Interests: Authors MS and HC are employees of the company Nanjing Dinfectome Technology Inc., China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shen, Liu, Shen, Zhang, Chen, Chen, Wang, Liu, Tao, He, Lu and Yan.)

Background: Degradation of the endothelial glycocalyx is critical for sepsis-associated lung injury and pulmonary vascular permeability. We investigated whether sulodexide, a precursor for the synthesis of glycosaminoglycans, plays a biological role in glycocalyx remodeling and improves endothelial barrier dysfunction in sepsis., Methods: The number of children with septic shock that were admitted to the PICU at Children's Hospital of Fudan University who enrolled in the study was 28. On days one and three after enrollment, venous blood samples were collected, and heparan sulfate, and syndecan-1 (SDC1) were assayed in the plasma. We established a cell model of glycocalyx shedding by heparinase III and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Sulodexide was administrated to prevent endothelial glycocalyx damage. Endothelial barrier function and expression of endothelial-related proteins were determined using permeability, western blot and immunofluorescent staining. The survival rate, histopathology evaluation of lungs and wet-to-dry lung weight ratio were also evaluated., Results: We found that circulating SDC1 levels were persistently upregulated in the non-alive group on days 1 and 3 and were positively correlated with IL-6 levels. Receiver operating characteristic curve analysis showed that SDC1 could distinguish patients with mortality. We showed that SDC1-shedding caused endothelial permeability in the presence of heparinase III and sepsis conditions. Mechanistically, sulodexide (30 LSU/mL) administration markedly inhibited SDC1 shedding and prevented endothelial permeability with zonula occludens-1 (ZO-1) upregulation via NF-κB/ZO-1 pathway. In mice with LPS and CLP-induced sepsis, sulodexide (40 mg/kg) administration decreased the plasma levels of SDC1 and increased survival rate. Additionally, sulodexide alleviated lung injury and restored endothelial glycocalyx damage., Conlusions: In conclusion, our data suggest that SDC1 predicts prognosis in children with septic shock and sulodexide may have therapeutic potential for the treatment of sepsis-associated endothelial dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ying, Zhang, Wang, Liu, Yu, Wang, Chen, Zhou and Lu.)

Introduction: The increasing prevalence of carbapenem-resistant gram-negative bacilli infection has emerged as a substantial threat to human health., Methodology: In January 2017, a screening program for carbapenem-resistant gram-negative bacilli colonization was performed in a pediatric intensive care unit (PICU). Subsequently, different strategies for carbapenem-resistant gram-negative bacilli cohorting and patient placements were introduced in January 2018., Results: The increase in the single room isolation (type A) and the resettlement of the same area placement (type B) resulted in a significant decrease in the nosocomial infection rate from 2.57% (50/1945) in 2017 to 0.87% (15/1720) in 2021 ( P  < 0.001). Notably, the incidence of nosocomial carbapenem-resistant gram-negative bacilli infections decreased in 2019 ( P  = 0.046) and 2020 ( P  = 0.041) compared with that in the respective previous year. During 2019 and 2020, a statistically significant increasing trend of type A and type B placements was observed ( P  < 0.05, each), which may have contributed to the decline of carbapenem-resistant gram-negative bacilli infection. The primary carbapenemase genes identified in carbapenem-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii were bla KPC-2 from sequence type 11 and bla OXA-23 from sequence type 1712., Conclusion: The integration of various placements for patients with carbapenem-resistant gram-negative bacilli infection with active screening has been demonstrated as an effective preventive strategy in the management of carbapenem-resistant gram-negative bacilli infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

We retrospectively investigated CRKP isolates among 92 pediatric patients (32 neonates and 60 non‑neonates) in 2019 and 2020 (59 and 33 isolates, respectively) to investigate the molecular characteristics and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from pediatric patients,. All the CRKP isolates were subjected to antimicrobial susceptibility testing, string testing, molecular typing of virulence and carbapenemase genes, and multilocus sequence typing. Hypervirulent K. pneumoniae (Hvkp) was defined based on the detection of the regulator of mucoid phenotype A (rmpA).Sequence type 11 (ST11) accounted for the majority of infections in both neonates (37.5%) and non‑neonates (43.3%) (P > 0.05), whereas it increased from 30.5% (18/59) in 2019 to 60.6% (20/33) in 2020 (P < 0.05). Carbapenemase gene KPC-2 was predominant in both neonates and non‑neonates (46.9% vs. 51.7%, respectively), followed by New Delhi metallo-beta-lactamase 1 (NDM-1) (34.4% vs. 28.3%, respectively) (all P > 0.05). Compared to 2019, the proportion of bla NDM-1 decreased (44.1% vs. 6.1%) (P < 0.001), while that of bla KPC-2 increased (40.7% vs. 66.7%) (P = 0.017) in 2020. ybtS and iutA had a higher positivity rate in KPC-2 and ST11 producers (all P < 0.05); the KPC-2-, ybtS-, and iutA-positive isolates showed relatively higher resistance to fluoroquinolones and aminoglycosides, nitrofurantoin, and piperacillin/tazobactam, respectively. Furthermore, the combined expression (95.7%, 88/92) of carbapenemase and virulence-associated genes was detected, with the carbapenemase genes bla KPC-2 and bla TEM-1 combined with virulence-associated genes entB, mrkD, and ybtS accounting for the highest percentage (20.7%).Carbapenemase gene mutations in the CRKP strain from 2019 to 2020 highlight the importance of dynamic monitoring. The spread of hypervirulence-associated genes in CRKP strains and the high positivity rates of ybtS and iutA in KPC-2- and ST11-producing ones signify their high virulence potential in pediatric patients., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium . Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment ( P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice ( P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium -induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest, financial or otherwise, related to the publication of this article., (© 2023 the author(s), published by De Gruyter.)

Metagenomic next-generation sequencing (mNGS) has shown promise in the diagnosis of infectious diseases in adults, while its efficacy in pediatric infections remains uncertain. We performed a retrospective analysis of 1,493 mNGS samples from pediatric patients with blood, central nervous system, and lower respiratory tract infections. The positive percent agreement (PPA) and the negative percent agreement (NPA) of mNGS were compared to conventional microbiological tests (CMT) based on clinical diagnosis. The agreement of mNGS compared to CMT, as well as the clinical impact of mNGS, were valuated. Using the clinical diagnosis as a reference, mNGS demonstrated a significantly higher overall PPA compared to CMT (53.1% [95% CI = 49.7 to 56.6%] versus 25.8% [95% CI = 22.8 to 28.9%]), while maintaining a comparable overall NPA (93.2% [95% CI = 91.3 to 95.1%] versus 97.2% [95% CI = 95.9 to 98.4%]). In septic patients under 6 years of age or with immunosuppressive status, mNGS showed a higher PPA and a comparable NPA compared to CMT. The overall PPA and NPA of mNGS compared to CMT were 75.3 and 75.0%, respectively. The majority of cases of Streptococcus pneumoniae, Streptococcus agalactiae, Mycobacterium tuberculosis complex, and Pneumocystis jirovecii infections were identified by mNGS. A positive clinical impact of 14.0% (206/1,473), a negative impact of 0.8% (11/1,473), a nonimpact of 84.7% (1,248/1,473), and an unknown impact of 0.5% (8/1,473) were observed in the mNGS results. Notably, the positive impact was greater among immunosuppressed patients than among nonimmunosuppressed individuals (67/247, 27.1% versus 139/1,226, 11.3%; P <  0.001). mNGS is valuable for pathogen detection, diagnosis, and clinical management of infections among pediatric patients. mNGS was thus effective for the diagnosis of pediatric infections, which may guide clinical management. Patients with immunosuppressive conditions benefited more from mNGS testing., Competing Interests: The authors declare no conflict of interest.

Background: Carbapenem-resistant gram-negative bacilli (CR-GNB) have been increasingly reported in China. However, dynamic monitoring data on molecular epidemiology of CR-GNB are limited in pediatric patients., Results: 300 CR-GNB isolates (200 Carbapenem-resistant K. pneumoniae (CRKP), 50 carbapenem-resistant A.baumannii (CRAB) and 50 carbapenem-resistant P. aeruginosa (CRPA)) were investigated. The predominant carbapenemase gene was bla NDM-1 (73%) and bla KPC-2 (65%) in neonates and non-neonates. Meanwhile, the predominant STs were ST11 (54%) in neonates and ST17 (27.0%) and ST278 (20.0%) in non-neonates. Notably, a shift in the dominant sequence type of CRKP infections from ST17 /ST278-NDM-1 to ST11-KPC-2 was observed during the years 2017-2021 and KPC-KP showed relatively higher resistance to aminoglycosides and quinolones than NDM-KP.Bla OXA-23 was isolated from all the CRAB isolates while only one isolate expressing bla BIC and 2 isolates expressing bla VIM-2 were found in CRPA isolates. ST195 (22.0%) and ST244 (24.0%) were the most common in CRAB and CRPA isolates and all the STs of CRAB belonged to CC92 while CRPA presents ST types with diversity distribution., Conclusion: CRKP showed different molecular phenotypes in neonates and non-neonates and was changing dynamically and high-risk clone of ST11 KPC-KP should be paid more attention. Most CRKP and CRAB strains shared the same CCs, suggesting that intrahospital transmission may occur, and large-scale screening and more effective measures are urgently needed., (© 2023. The Author(s).)

Background: Notch signaling is critical for regulating the function of vascular endothelial cells (ECs). However, the effect of the intracellular domain of Notch1 (NICD) on EC injury in sepsis remains unclear., Methods: We established a cell model of vascular endothelial dysfunction and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Endothelial barrier function and expression of endothelial-related proteins were determined using CCK-8, permeability, flow cytometry, immunoblot, and immunoprecipitation assays. The effect of NICD inhibition or activation on endothelial barrier function was evaluated in vitro . Melatonin was used for NICD activation in sepsis mice. The survival rate, Evans blue dye of organs, vessel relaxation assay, immunohistochemistry, ELISA, immunoblot were used to explore the specific role of melatonin for sepsis induced vascular dysfunction in vivo ., Results: We found that LPS, interleukin 6, and serum collected from septic children could inhibit the expression of NICD and its downstream regulator Hes1, which impaired endothelial barrier function and led to EC apoptosis through the AKT pathway. Mechanistically, LPS decreased the stability of NICD by inhibiting the expression of a deubiquitylating enzyme, ubiquitin-specific proteases 8 (USP8). Melatonin, however, upregulated USP8 expression, thus maintaining the stability of NICD and Notch signaling, which ultimately reduced EC injury in our sepsis model and elevated the survival rate of septic mice., Conclusions: We found a previously uncharacterized role of Notch1 in mediating vascular permeability during sepsis, and we showed that inhibition of NICD resulted in vascular EC dysfunction in sepsis, which was reversed by melatonin. Thus, the Notch1 signaling pathway is a potential target for the treatment of sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhang, Ying, Wang, Yan, Zhou and Lu.)

Objective: The number of children on prolonged mechanical ventilation (PMV) in pediatric intensive care units (PICU) has increased markedly, but little is known about the situation in mainland China. We carried out a multicenter retrospective investigation to describe the clinical characteristics and prognosis of Chinese children receiving long-term ventilation in the PICU., Methods: A retrospective study was performed in 11 PICUs. All participating patients with prolonged mechanical ventilation in the study were retrospectively identified and included from cases admitted to PICUs between January 1, 2017 and December 31, 2019., Results: A total of 346 children diagnosed with prolonged mechanical ventilation were included in the study. Overall, 240 survived and were discharged from PICU, 55 died in hospital, and 51 withdrew from mechanical ventilation support with 41 died after discharge. Lower airway diseases were the most common underlying causes (41.6%), followed by central nervous system diseases (29.5%), and neuromuscular diseases (13.3%). Most children (327, 94.5%) received invasive mechanical ventilation (IMV) and only 19 (5.5%) children received noninvasive ventilation (NIV). The median time of tracheostomy after ventilation was 21 days (15-35). Children with tracheostomy had lower mortality with longer PICU stay compared with patients without tracheostomy. Children who underwent tracheostomy were more likely to have central nervous system diseases and neuromuscular diseases., Conclusion: This study showed a steady increase in the number of children receiving prolonged mechanical ventilation during the study period in Chinese PICUs with distinct clinical characteristics and outcomes. A better community-based care for PMV children is needed in mainland China., (© 2023 Wiley Periodicals LLC.)

Background: Understanding the occurrence and severity of child injuries is the cornerstone of preventing child injuries. Currently, there is no standardized child injury surveillance dataset in China., Methods: Multistage consultation by a panel of Chinese experts in child injury to determine items to include in the core dataset (CDS) was performed. The experts participated in two rounds of the modified Delphi method comprising a consultation questionnaire investigation (Round 1) and a face-to-face panel discussion (Round 2). Final consensus was established based on the opinions of the experts regarding the modified CDS information collection items. Enthusiasm and authority exhibited by the experts were evaluated by the response rate and using the expert authority coefficient, respectively., Results: The expert panel included 16 experts in Round 1 and 15 experts in Round 2. The experts during both rounds had a high degree of authority, with an average authority coefficient of 0.86. The enthusiasm of the experts was 94.12%, and the proportion of suggestions reached 81.25% in Round 1 of the modified Delphi method. The draft CDS evaluated in Round 1 included 24 items, and expert panelists could submit recommendations to add items. Based on findings in Round 1, four additional items, including nationality, residence, type of family residence, and primary caregiver were added to the draft of the CDS for Round 2. After Round 2, consensus was reached on 32 items arranged into four domains-general demographic information, injury characteristics, clinical diagnosis and treatment, and injury outcome-to include in the final CDS., Conclusion: The development of a child injury surveillance CDS could contribute to standardized data collection, collation, and analysis. The CDS developed here could be used to identify actionable characteristics of child injury to assist health policymakers in designing evidence-based injury prevention interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gong, Wang, Li, Ye, Xie, Lu, Liu, Song, Zhai, Xu and Duan.)

Background: The concept of acute kidney injury (AKI) substages has been recommended to better phenotype AKI and identify high-risk patient groups and therefore improve the diagnostic accuracy of AKI. However, there remains a gap between the recommendation and the clinical application. The study aimed to explore the incidence of AKI substages based on a sensitive AKI biomarker of urinary cystatin C (uCysC), and to determine whether AKI substages were relevant with respect to outcome in critically ill children., Results: The multicenter cohort study enrolled 793 children in pediatric intensive care unit (PICU) of four tertiary hospitals in China. Children were classified as non-AKI, sub-AKI and AKI substages A and B according to uCysC level at PICU admission. Sub-AKI was defined by admission uCysC level ≥ 1.26 mg/g uCr in children not meeting the KDIGO criteria of AKI. In children who fulfilled KDIGO criteria, those with uCysC < 1.26 was defined as AKI substage A, and with ≥ 1.26 defined as AKI substage B. The associations of AKI substages with 30-day PICU mortality were assessed. 15.6% (124/793) of patients met the definition of sub-AKI. Of 180 (22.7%) patients with AKI, 90 (50%) had uCysC-positive AKI substage B and were more likely to have classical AKI stage 3, compared to substage A. Compared to non-AKI, sub-AKI and AKI substages A and B were risk factors significantly associated with mortality, and the association of sub-AKI (adjusted hazard ratio HR = 2.42) and AKI substage B (adjusted HR = 2.83) with mortality remained significant after adjustment for confounders. Moreover, AKI substage B had increased risks of death as compared with sub-AKI (HR = 3.10) and AKI substage A (HR = 3.19)., Conclusions: Sub-AKI defined/based on uCysC occurred in 20.2% of patients without AKI and was associated with a risk of death close to patients with AKI substage A. Urinary CysC-positive AKI substage B occurred in 50% of AKI patients and was more likely to have classical AKI stage 3 and was associated with the highest risk of mortality., (© 2023. The Author(s).)

Background: Severe pneumonia due to lower respiratory tract infections (LRTIs) is a significant cause of morbidity and mortality in children. Noninfectious respiratory syndromes resembling LRTIs can complicate the diagnosis and may also make targeted therapy difficult because of the difficulty of identifying LRTI pathogens. In the present study, a highly sensitive metagenomic next-generation sequencing (mNGS) approach was used to characterize the microbiome of bronchoalveolar lavage fluid (BALF) in children with severe lower pneumonia and identify pathogenic microorganisms that may cause severe pneumonia. The purpose of this study was to use mNGS to explore the potential microbiomes of children with severe pneumonia in a PICU., Methods: We enrolled patients meeting diagnostic criteria for severe pneumonia admitted at PICU of the Children's Hospital of Fudan University, China, from February 2018 to February 2020. In total, 126 BALF samples were collected, and mNGS was performed at the DNA and/or RNA level. The pathogenic microorganisms in BALF were identified and correlated with serological inflammatory indicators, lymphocyte subtypes, and clinical symptoms., Results: mNGS of BALF identified potentially pathogenic bacteria in children with severe pneumonia in the PICU. An increased BALF bacterial diversity index was positively correlated with serum inflammatory indicators and lymphocyte subtypes. Children with severe pneumonia in the PICU had the potential for coinfection with viruses including Epstein-Barr virus, Cytomegalovirus , and Human betaherpesvirus 6B , the abundance of which was positively correlated with immunodeficiency and pneumonia severity, suggesting that the virus may be reactivated in children in the PICU. There was also the potential for coinfection with fungal pathogens including Pneumocystis jirovecii and Aspergillus fumigatus in children with severe pneumonia in the PICU, and an increase in potentially pathogenic eukaryotic diversity in BALF was positively associated with the occurrence of death and sepsis., Conclusions: mNGS can be used for clinical microbiological testing of BALF samples from children in the PICU. Bacterial combined with viral or fungal infections may be present in the BALF of patients with severe pneumonia in the PICU. Viral or fungal infections are associated with greater disease severity and death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liu, Wang, Chen, Liu, Tao, Zhang, Zhu, Zhang, Ming, Wang, Lu and Yan.)

Objectives: To reveal the clinical and molecular characteristics of Bordetella pertussis (BP) prevalent in Shanghai, China., Methods: A total of 9430 children with suspected pertussis from 2021 to 2022 were included, and nasopharyngeal swab samples were collected for polymerase chain reaction detection, culture, antimicrobial susceptibility testing, and 23S rRNA gene A2047G detection. BP strains were typed using multilocus variable-number tandem-repeat analysis and virulence genotyping., Results: Of 9430 cases, 5.1% and 1.6% were confirmed by polymerase chain reaction and culture, respectively. Infants (aged <1 year) accounted for 24.7% and presented much more severe symptoms than noninfants. Pertussis was most frequently detected in infants aged 0-6 months (11.3∼14.0%) and children aged >6-10 years (10.8∼21.7%). Macrolide-resistant BP (MRBP) accounted for 89.3%, and all carried the A2047G mutation. There were six multilocus variable-number tandem-repeat analysis types (MTs), including MT28 (62.0%), MT195 (20%), MT27 (10.0%), MT104 (4.7%), MT55 (2.7%), and MT32 (0.7%). BP strains with pertussis toxin (ptx)P3/(pertactin) prn2/ptxC2/ptxA1/(fimbrial proteins) fim2-1/fim3-1, including MT27, MT28, and MT32, accounted for 72.7%, among which MT27 and MT32 were macrolide-sensitive BP, whereas most (94.6∼100%) of MT28 were MRBP. Strains harboring ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1, including MT55, MT104, and MT195, belonged to macrolide-sensitive BP., Conclusion: The emergence and spread of MT28 ptxP3-MRBP was first reported in China, highlighting the importance of continuous surveillance of ptxP3-MRBP to prevent its potential circulation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Characterized by rapid transmission but lower severity, the new Omicron wave brought about an acute increase in local corona virus disease 2019 (COVID-19) cases in Shanghai, followed by stricter infection prevention and control strategies. Inevitably, more time was required for emergency consultation and treatment of children with critical illnesses. Therefore, a multidimensional approach was designed to streamline the emergency service and reduce the incidence of nosocomial infection of sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron wave for the emergency department (ED) at the Children's Hospital of Fudan University (CHFU)., Methods: A multidimensional approach was implemented in the ED to help achieve a balance between the demand for emergency services and pandemic control, consisting of ED layout adjustment; electronic screening (E-screening) measures; standard management processes for patients, medical staff, and goods transfer; reliable disinfection measures; and a surveillance system for infection prevention and control. To evaluate the effect of the management strategy, the data on nosocomial infection cases and occupational exposure episodes among staff in the ED were collected. The demographic and clinical characteristics of level I/II children by the five-level pediatric triage tool and their mean duration of stay in the resuscitation room were collected., Results: There were 12,114 ED visitors from March 1 to May 31 in 2022, among which 53.24% were medical emergencies (6,449/12,114) and 46.76% were surgical emergencies (5,665/12,114). Twenty-nine patients were sent to the buffer zone, four of whom were transferred to the pediatric intensive care unit (PICU) because of the critical situation. Six patients tested positive for COVID-19 after entering ED, including three in the buffer zone and three in the ED clinic, causing a temporary closure of the ED for disinfection. There were no reports on medical care delays, unintended deaths, staff with COVID-19 infection, or occupational exposures to COVID-19., Conclusions: Our findings highlight the effectiveness of the multidimensional approach, which can simultaneously meet the emergency care needs of patients as well as pandemic prevention and control. However, the results were obtained against the proportional decrease in clinic visitors due to the Shanghai lockdown. Dynamic assessment and further optimization may be adopted to cope with the pre-pandemic visit volume., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-314/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest to report.

Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.

Introduction: To examine the in vitro and in vivo antimicrobial activities of ceftazidime/avibactam (CZA) alone or in combination with aztreonam (ATM) against KPC-, NDM-, IMP-, KPC+IMP-, KPC+NDM-producing strains., Methods: A total of 67 clinical non-repetitive carbapenem-resistant Enterobacterales (CRE) strains were selected for the microdilution broth method that was performed to analyze the minimal inhibitory concentration (MIC) and the combination antimicrobial susceptibility test using checkerboard titration method. The fractional inhibitory concentration (FIC) was calculated to determine the antimicrobial effect. The time-kill assays and the mouse infection model were used to study the bactericidal effect and therapeutic effect of CZA alone or in combination with ATM., Results: The CZA minimal inhibitory concentration (MIC) values of CZA revealed that 29 KPC-producing strains and 1 OXA-producing strain were ≤4µg/mL. The CZA MIC values of 37 metal-β-lactamase (MBLs)-producing strains such as NDM-, IMP-, KPC+IMP-, KPC+NDM-producing strains were ≥128µg/mL, after combining with ATM, the FIC values were all below 0.51. The time-kill assays revealed that CZA at various concentrations of 2, 4 and 8 MIC showed significant bactericidal efficiency to the KPC-producing strains. For NDM-, IMP-producing strains, no colony growth was detected after 8 hours of incubation with CZA in combination with ATM. Six percent of the mice in the treatment group and 58% of the mice in the infection group died within 3 days., Conclusion: Our in vitro results showed that CZA had a good antimicrobial effect on the KPC-producing and OXA-producing strains. CZA combined with ATM showed synergistic bacteriostatic or bactericidal activity against NDM-, IMP-, KPC+IMP-, KPC+NDM-producing strains. The combination of CZA and ATM reduced mortality and prolonged lifespan of mice infected with NDM-, IMP-, KPC+IMP-, and KPC+NDM-producing strains, which provides fundamental knowledge for improving treatment strategies and initializing clinical trials., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Lu et al.)

With the rapid development of the nano-material and chemical industry, more and more microplastic (MP) and nano-material were discharged into the environment. In this study, a two-dimensional (2D) surface of Extended Darjaguin-Landau-Verwe-Overbeek (XDLVO) is proposed to quantitatively investigate the effect of polyamide (PA) on the transport of graphene oxide (GO) in porous media. The influences of mass fraction of PA, flow rate, GO concentration, ionic type and strength on the migration of GO in saturated porous media are investigated by column experiments and numerical models. The two-dimensional (2D) surfaces of XDLVO interaction energy between GO and GO, GO and QS, GO and PA, are firstly calculated to analyze the transport of GO in saturated porous media. Experimental results suggest the mobility of GO is enhanced when flow velocity and initial concentration of GO are increased. However, the mobility of GO is inhibited when the mass fraction of PA and ionic strength are increased. More important, the inhibitory effect of divalent cations on GO migration is stronger than that of monovalent cations. Simultaneously, XDLVO results suggest that ionic types and strengths are important factors affecting the mobility of GO in porous media, and the critical ionic strength is observed from the continuous variation of the secondary minimum trap of XDLVO interaction energy. Model results show that there is a linear relationship between the logarithm of the secondary minimum trap of XDLVO interaction energy and the parameters related to GO mobility, which suggests XDLVO energy surface has an important application significance in the accurate quantification of GO mobility in porous media. These findings contribute to GO transport affected by microplastic in porous media, thus laying a significant foundation for the environmental risk and contamination remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this article, we study the finite-time stabilization and the asymptotic stabilization with probability one of Markovian jump Boolean control networks (MJBCNs) by sampled-data state feedback controls (SDSFCs). Based on the semi-tensor product (STP), we introduce an augmented variable multiplied by the vector form of the switching signal and the state of MJBCN. We find that under SDSFC, the sequence of the states of the augmented variable at sampling instants satisfies the Markov property. Based on the convergences of the switching signal and the augmented variable, we obtain the sufficient and necessary criteria for the finite-time stabilization and the asymptotic stabilization of MJBCNs by SDSFCs, respectively. Moreover, for the two kinds of stabilization, the feedback matrices of SDSFCs are constructed, respectively. Finally, the obtained results are applied to an apoptosis network and a model of the lactose operon in the Escherichia Coli.

Introduction: Multiple organ dysfunction syndrome (MODS) with secondary hemophagocytic lymphohistiocytosis (SHLH) causes significant mortality. We aimed to identify the predictor factors for death in pediatric patients with SHLH-associated MODS receiving continuous renal replacement therapy (CRRT)., Methods: This multicentered nested case-control study was conducted from 2016 to 2020. The characteristics were compared between survivors and non-survivors. Logistic regression was applied to identify the risk factors for death. The cutoff values were assessed by receiver operating characteristics curves., Results: Fifty two patients were enrolled in this study. Interleukin-6 level (p = 0.018) and the number of organ dysfunction (p = 0.047) were independent risk factors for death. The cutoff value of 13.12 pg/ml interleukin-6 and three organs dysfunction at CRRT initiation presented a high sensitivity and specificity., Conclusion: The number of organ dysfunction and interleukin-6 at CRRT initiation are independent risk factors for death in pediatric patients with SHLH-associated MODS., (© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Objective: To explore the value of pediatric early warning scoring system (PEWS) in an emergency observation room in China., Methods: The children who had been admitted consecutively to the emergency observation room from Jan, 2019 to Aug, 2020 were selected. Three most important time-points including the first value (admission value), the highest value during the observation (highest value), and final value (discharge value) of Brighton Pediatric Early Warning Score (PEWS) was evaluated in all patients., Results: 4717 patients were included. They were categorized into 3 groups, namely, discharged group (G1, n = 2320), specialized ward group (G2, n = 2128), and ICU group (G3, n = 269). The different PEWS values of admission value, highest value, and discharge value were significantly different among the 3 groups (P<0.001). Highest value of G1 and G2 were significantly lower than that of G3 (P<0.001). AUROC curves of different PEWS values were used to predict the possibility of PICU admission and PICU mortality within 24 h of admission, and the values were 0.698, 0.878, 0.974 and 0.709, 0.883, 0.951, respectively. The cutoff values for PICU admission of 3 different PEWS values were 2.5 (sensitivity 0.635, specificity 0.699), 3.5 (sensitivity 0.817, specificity 0.9), 3.5 (sensitivity 0.837, specificity 0.985). The cutoff values for PICU mortality of 3 different PEWS values were 4 (sensitivity 0.625, specificity 0.799), 4.5 (sensitivity 0.722, specificity 0.79), 4.5 (sensitivity 0.883, specificity 0.987). The discharge value had the strongest prediction ability., Conclusions: PEWS can be used for early identification and warning of critically ill children., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Microplastics are widely detected in the soil-groundwater environment, which has attracted more and more attention. Clay mineral is an important component of the porous media contained in aquifers. The transport experiments of polystyrene nanoparticles (PSNPs) in quartz sand (QS) mixed with three kinds of clay minerals are conducted to investigate the effects of kaolinite (KL), montmorillonite (MT) and illite (IL) on the mobility of PSNPs in groundwater. Two-dimensional (2D) distributions of DLVO interaction energy are calculated to quantify the interactions between PSNPs and three kinds of clay minerals. The critical ionic strengths (CIS) of PSNPs-KL, PSNPs-MT and PSNPs-IL are 17.0 mM, 19.3 mM and 21.0 mM, respectively. Experimental results suggest KL has the strongest inhibition effect on the mobility of PSNPs, followed by MT and IL. Simultaneously, the change of ionic strength can alter the surface charge of PSNPs and clay minerals, thus affecting the interaction energy. Experimental and model results indicate both the deposition rate coefficient (k) and maximum deposition (S max ) linearly decrease with the logarithm of the DLVO energy barrier, while the mass recovery rate of PSNPs (R m ) exponentially increases with the logarithm of the DLVO energy barrier. Therefore, the mobility and associated kinetic parameters of PSNPs in complex porous media containing clay minerals can be predicted by 2D distributions of DLVO interaction energy. These findings could help to gain insight into understanding the environmental behavior and transport mechanism of microplastics in the multicomponent porous media, and provide a scientific basis for the accurate simulation and prediction of microplastic contamination in the groundwater system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Understanding the fate and transport of polystyrene nanoparticles (PSNPs) in porous media under various conditions is necessary for evaluating and predicting environmental risks caused by microplastics. The transport kinetics of PSNPs are investigated by column experiment and numerical model. The surface of DLVO interaction energy is calculated to analyze and predict the adsorption and aggregation of PSNPs in porous media, which the critical ionic strength of PSNPs can be accurately investigated. The results of the DLVO energy surface suggest that when the concentration of Na + increases from 1 mM to 50 mM, the DLVO energy barrier of PSNPs-silica sand (SS) decreases from 78.37 kT to 5.46 kT. As a result, PSNPs are easily adsorbed on the surface of SS and the mobility of PSNPs is reduced under the condition of a high concentration of Na + (PSNPs recovery rate decreases from 62.16% to 3.65%). When the concentration of Ca 2+ increases from 0.1 mM to 5 mM, the DLVO energy barrier of PSNPs-SS decreases from 12.10 kT to 1.90 kT, and PSNPs recovery rate decreases from 82.46% to 4.27%. Experimental and model results showed that PSNPs mobility is enhanced by increasing initial concentration, flow velocity and grain size of SS, while the mobility of PSNPs with larger particle diameter is lower. Regression analysis suggests that kinetic parameters related to PSNPs mobility are correlated with DLVO energy barriers. The environmental behavior and mechanism of PSNPs transport in porous media are further investigated in this study, which provides a scientific basis for the systematic and comprehensive evaluation of the environmental risk and ecological safety of nano-plastic particles in the groundwater system., (Copyright © 2022. Published by Elsevier Inc.)

Background: Substantial interstudy heterogeneity exists in defining acute kidney injury (AKI) and baseline serum creatinine (SCr). This study assessed AKI incidence and its association with pediatric intensive care unit (PICU) mortality under different AKI and baseline SCr definitions to determine the preferable approach for diagnosing pediatric AKI., Methods: In this multicenter prospective observational cohort study, AKI was defined and staged according to the Kidney Disease: Improving Global Outcome (KDIGO), modified KDIGO, and pediatric reference change value optimized for AKI (pROCK) definitions. The baseline SCr was calculated based on the Schwartz formula or estimated as the upper normative value (NormsMax), admission SCr (AdmSCr) and modified AdmSCr. The impacts of different AKI definitions and baseline SCr estimation methods on AKI incidence, severity distribution and AKI outcome were evaluated., Results: Different AKI definitions and baseline SCr estimates led to differences in AKI incidence, from 6.8 to 25.7%; patients with AKI across all definitions had higher PICU mortality ranged from 19.0 to 35.4%. A higher AKI incidence (25.7%) but lower mortality (19.0%) was observed based on the Schwartz according to the KDIGO definition, which however was overcome by modified KDIGO (AKI incidence: 16.3%, PICU mortality: 26.1%). Furthermore, for the modified KDIGO, the consistencies of AKI stages between different baseline SCr estimation methods were all strong with the concordance rates > 90.0% and weighted kappa values > 0.8, and PICU mortality increased pursuant to staging based on the Schwartz. When the NormsMax was used, the KDIGO and modified KDIGO led to an identical AKI incidence (13.6%), but PICU mortality did not differ among AKI stages. For the pROCK, PICU mortality did not increase pursuant to staging and AKI stage 3 was not associated with mortality after adjustment for confounders., Conclusions: The AKI incidence and staging vary depending on the definition and baseline SCr estimation method used. The modified KDIGO definition based on the Schwartz method leads AKI to be highly relevant to PICU mortality, suggesting that it may be the preferable approach for diagnosing AKI in critically ill children and provides promise for improving clinicians' ability to diagnose pediatric AKI., (© 2022. The Author(s).)

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and unclear etiology. Vagus nerve stimulation (VNS) is an FDA-approved therapy for refractory epilepsy that has been shown to decrease the frequency and severity of seizures. There is a growing interest in alternate non-pharmaceutical therapies for managing super-refractory status epilepticus (SRSE). We present a 29-month-old case, diagnosed with FIRES, whose seizures were successfully controlled by utilization of VNS after ineffective response to intensive pharmacotherapy and ketogenic diet treatment. The VNS was planted after 14 days of refractory seizure activity with a following rapid parameter titration for 42 days without evident side effect, which finally controlled the seizure in the acute phase. VNS may be a potential candidate for the treatment of SRSE in FIRES., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A new type of asymptotic stability for nonlinear hybrid neutral stochastic systems with constant delays was investigated recently, where the criteria depended on the delays' sizes. Unfortunately, developed theory so far is not sufficient to deal with challenging problems of the decay rate, time-varying delays, and nonautonomous issues. These problems have not been tackled in the existing literature. Consequently, under the weak constraints, this article focuses on the general decay, including the exponential stability and the polynomial stability, for nonlinear nonautonomous hybrid neutral stochastic systems with time-varying delays by the approach of the multiple degenerate functionals. Moreover, this article derives the interesting assertions related to the general H ∞ stability and the polynomial growth at most.