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Introduction: The recently developed DOT-MGA (direct-on-target microdroplet growth assay) has shown the desirability of direct application of this approach in positive blood cultures and its good performance in detection. This study selected 44 Enterobacteriaceae strains and implemented a DOT-MGA assay on blood cultures to detect their resistance to seven antibiotics. The results of DOT-MGA were compared with the other two antimicrobial susceptibility testing (AST) methods to analyze the detection performance of DOT-MGA., Methods: We adopted the differential centrifugation to process positive blood-culture (BC). Processed BC broth was directly used for rapid AST using DOT-MGA. Droplets of 6 µL with and without antibiotics at the EUCAST breakpoint concentration were spotted in triplicates onto the surface of a MALDI target. The plates were incubated in a wet box for 4 h before the broth was removed with filter paper. Bruker Biotyper software was used to analyze the test results compared with standard database, and the scores were used to quantify and determine the results., Results: DOT-MGA results were compared with the direct-from-BC disk-diffusion method and results were reported by broth microdilution method, respectively. The comparison demonstrated a 100% growth efficiency in DOT-MGA, a 100% classification consistency for ampicillin, ceftriaxone, and gentamicin, and >93% classification consistency for tobramycin, aztreonam, trimethoprim-sulfamethoxazole (TMP-SMX), and ceftazidime., Discussion: These study results have shown that DOT-MGA is suitable for directly identifying bacterial resistance to positive blood cultures in clinical microbiology laboratories. Furthermore, it is conducive for early diagnosis and treatment of patients with bloodstream infection due to its convenience, time efficiency, and good performance in identifying multiple antibiotic-insensitive bacteria., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Tang et al.)

Objectives: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants., Design: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019., Setting: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved., Participants: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations)., Interventions: None., Measurements and Main Results: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist., Conclusions: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Herein, we describe pH-responsive Pickering emulsions stabilized by a sodium carboxylate-derived selenium surfactant (C 10 -Se-C 10 ·(COONa) 2 ) in combination with positively charged alumina nanoparticles. Unlike other bola-type carboxylate surfactants (e.g., disodium eicosanoate), C 10 -Se-C 10 ·(COONa) 2 is soluble in water with a low Krafft temperature (36.1 °C). The emulsions are sensitive to pH variations, and efficient demulsification can be achieved by a pH trigger. The carboxylic sodium group in the C 10 -Se-C 10 ·(COONa) 2 structure can be reversibly cycled between its anionic and nonionic states (carboxylic acid), resulting in a pH-controlled electrostatic attraction between the surfactant and alumina. The Pickering emulsion can be reversibly switched between "on" (stable) and "off" (unstable) states by pH at least four times. Compared with the emulsions stabilized by specially synthesized stimuli-responsive particles or surfactants, the method reported here is much easier to implement and requires very low concentrations of the surfactant and nanoparticles, with potential applications in the fields of biomedicine, drug delivery, and cosmetics.

Objectives: To develop a population pharmacokinetic model of meropenem in children with sepsis receiving extracorporeal life support (ECLS) and optimize the dosage regimen based on investigating the probability of target attainment (PTA). Methods: The children with sepsis were prospectively enrolled in a pediatric intensive care unit from January 2018 to December 2019. The concentration-time data were fitted using nonlinear mixed effect model approach by NONMEM program. The stochastic simulation considering various scenarios based on proposed population pharmacokinetics model were conducted, and the PTAs were calculated to optimize the dosage regimens. Results: A total of 25 children with sepsis were enrolled, of whom13 received ECMO, 9 received CRRT, and 4 received ECMO combined with CRRT. 12 children received a two-step 3-h infusion and 13 children received 1-h infusion. Bodyweight and creatinine clearance had significant impacts on the PK parameters. ECMO intervention was not related to the PK properties. If 100%T > MIC was chosen as target, children receiving 40 mg/kg q8h over a 3 h-infusion only reached the PTA up to 77.4%. If bacteria with MIC 2 mg/L were to be treated with meropenem and the PTA target was 50%T > MIC, a dose of 40 mg/kg q8h for 1 h infusion would be necessary. Conclusions: The PK properties of meropenem in septic children receiving extracorporeal life support were best described. We recommended the opitimized dosing regimens for septic children receiving ECLS depending on the PTA of PK target 50%T > MIC and 100%T > MIC, for children with sepsis during ECLS with different body weight, estimated creatinine clearance (eCRCL) and MIC of bacteria., 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 © 2021 Wang, Chen, Huang, Wang, Li, Yan, Chen and Lu.)

Bloodstream infection is a life-threatening complication in critically ill patients. Multi-drug resistant bacteria or fungi may increase the risk of invasive infections in hospitalized children and are difficult to treat in intensive care units. The purpose of this study was to use metagenomic next-generation sequencing (mNGS) to understand the bloodstream microbiomes of children with suspected sepsis in a pediatric intensive care unit (PICU). mNGS were performed on microbial cell-free nucleic acid from 34 children admitted to PICU, and potentially pathogenic microbes were identified. The associations of serological inflammation indicators, lymphocyte subpopulations, and other clinical phenotypes were also examined. mNGS of blood samples from children in PICU revealed potential eukaryotic microbial pathogens. The abundance of Pneumocystis jirovecii was positively correlated with a decrease in total white blood cell count and immunodeficiency. Hospital-acquired pneumonia patients showed a significant increase in blood bacterial species richness compared with community-acquired pneumonia children. The abundance of bloodstream bacteria was positively correlated with serum procalcitonin level. Microbial genome sequences from potential pathogens were detected in the bloodstream of children with suspected sepsis in PICU, suggesting the presence of bloodstream infections in these children., Competing Interests: Author YZ was employed by company BGI PathoGenesis Pharmaceutical Technology Co., Ltd. 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 © 2021 Yan, Liu, Chen, Chen, Cheng, Tao, Cai, Zhou, Wang, Wang and Lu.)

Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China. Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged <18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t -test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital. Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93-4.63, P < 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93-433.14, P < 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07-1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48-4.49, P < 0.001) had a significantly higher risk of admission. Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission., 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 © 2021 Gong, Lu, Ma, Zheng, Hu, Liu, Song, Hu, Sun, Chen, Xie, Zhang, Duan and Xu.)

Background: The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China., Methods: We conducted a retrospective case-control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019., Results: During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza., Conclusion: Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

The aim of this study was to establish the population pharmacokinetics (PK) model of Vancomycin for Chinese pediatric patients which can extrapolate to whole age periods by bridging the published adult population PK model and the established pediatric population PK model. The final consolidated population PK model was used to explore the correlation of pharmacokinetics/pharmacodynamics (PK/PD) indices and efficacy of vancomycin and to provide evidence for the optimized regimen of vancomycin in Chinese pediatric patients with Gram-positive bacterial infection. 108 pediatric patients with Gram-positive infections from 2 pediatric hospitals in China in the first period of the prospective multi-center vancomycin clinical observational study were enrolled to establish the population PK model. A one-compartment population PK model was established and validated. The correlation between vancomycin PK/PD indices [trough concentration (C min ), peak concentration (C max ), 0-24 h area under the curve (AUC 0-24 ) and the area under the curve to minimum inhibitory concentration ratio (AUC 0-24 /MIC)] and the overall clinical outcomes (clinical efficacy and microbiological efficacy) in Chinese pediatric patients were evaluated. There is no significant correlation between PK/PD indices and clinical efficacy or microbiological efficacy. Considering the high clinical effective rate (>90%) and median AUC 0-24 /MIC values of 200-300, Chinese pediatric patients with Gram-positive bacterial infection may be suitable for lower AUC 0-24 /MIC target value compared to the target value of 400-600 recommended by IDSA guideline. Different optimal dose regimen of vancomycin for Chinese pediatric patients should be considered. Further evaluation in more prospective studies will be needed., 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 © 2021 Shen, Fan, Yang, Chen, Tao, Lu, Zhang, Huang and Zhang.)

Background: The gut is thought to play an important role in the pathogenesis of sepsis. Changes in the gut microbiota are closely related to the occurrence and development of human diseases, but few studies have focused on taxonomic composition of gut microbiota in septic patients. Knowledge of changes in the gut microbiota is a key issue in intensive care. Clinicians must understand how an altered gut microbiota affects the susceptibility and prognosis of septic patients. Measurements and Main Results: In the single-center case control study, 20 septic patients and 20 healthy children were recruited. The taxonomic composition of gut microbiota was determined via 16S rRNA gene sequencing. Gut microbiota diversity in children with sepsis was significantly reduced compared with that in healthy children. The taxonomic composition of gut microbiota can effectively distinguish children with sepsis from healthy children. Thirteen taxa of gut microbiota were significantly increased in the guts of children with sepsis compared with those of healthy children. The increased abundances of Enterococcaceae, Enterococcus , and Enterococcus durans in gut of septic patients were significantly positively correlated with blood inflammation indicators CRP and WBC. The abundances of seven bacteria were significantly decreased in the guts of septic children compared with those of healthy children. The decreased abundance of Bifidobacteriales in gut of septic patients is significantly negatively correlated with blood inflammation index WBC. A machine-learning classifier was built for distinguishing sepsis and achieved the AUC value of 81.25%. It shows that the composition of gut microbiota has certain potential for diagnosis of sepsis. Conclusions: Gut microbiota alterations in septic patients exhibit proliferation of opportunistic pathogenic bacteria, the massive reduction of the commensal flora, and the significant decrease in the diversity of the gut microbiota. Dysbiosis may also account for some changes in the inflammation indexes., 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 © 2021 Liu, Wang, Chen, Ma, Peng, Zhang, Wang, Yan and Lu.)

Background: Understanding current hemodynamic monitoring (HM) practice patterns is essential to determine education and training strategies in China. The survey was to describe the practice of HM and management in children with septic shock in China., Methods: We conducted an Email-based survey of members of sub-association of pediatric intensive care physicians. The questionnaire consisted of 22 questions and gathered the following information: (I) general information on the hospitals, respective ICUs and participants, (II) the availability of technical equipment and parameters of HM and (III) management simulation of septic shock in three clinical case vignettes., Results: Surveys were received from 68 institutions (87.2%) and 368 questionnaires (response-rate 45.1%) were included. Basic HM (93-100%) were reported as the most utilized parameters, followed by advanced HM which included central venous pressure (CVP) (56.0%), cardiac output (53.5%), and central venous oxygen saturation (36.7%), 61.1% (225/368) of respondents stated the utilization of non-invasive HM equipment. The factors such as ICU specialist training center (P=0.003) and more than 30 cases of septic shock per year (P=0.002) were related to the utilization of non-invasive monitoring equipment. In the simulated case vignette, 49.7% (183/368) of respondents reported performing fluid responsiveness and volume status (FR-VS) assessment. Despite differences in training centers (P=0.005) and educational backgrounds (P=0.030), FR-VS assessment was not related to the volume expansion decision., Conclusions: There is a large variability in use advanced HM parameters, an increasing awareness and acceptance of non-invasive HM devices and a potential need for hemodynamic education and training in pediatric intensive care medicine in China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-374). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

To investigate the effect of normalized mutual information (MRI) image segmentation in accurate localization of prostate cancer with infection and the role in disease treatment, the normalized mutual information method is used to measure the similarity of images, so as to select the maps. Then, the popular global weighted voting method and normalized mutual information method are applied to calculate the weights and carry out the label image fusion. The map selection method based on mutual information substantially completes the segmentation of the MRI image prostate. The prostate position is basically found on the 10 test images, and the positioning of the prostate organs is deviated in the worst case. In the case of poor multi-map segmentation, it usually happens when those are not well represented in the map. Because of the structural similarity of medical images, multi-atlas segmentation based on normalized mutual information method can be done. Using the prior information of atlas, the atlas label image can be selected. After fusion, the final segmentation of the test image can be completed, which has a high accuracy for the location of prostate cancer. This method can accurately delineate the target area in radiotherapy of prostate cancer and reduce the damage of rectum, bladder and other organs caused by radiotherapy. However, there are still some problems in this study, such as inadequate segmentation accuracy, long data processing time and so on. There is still a certain distance from practicality, and further research is needed., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Code Blue is a popular hospital emergency code that is used to alert the emergency response team to any medical emergency requiring critical care. By retrospectively studying Code Blue cases in a children's hospital, we looked for high-risk factors associated with survival and how to improve the effectiveness of Code Blue systems through training., Methods: Data were collected on age, gender, department, diagnosis, time of Code Blue call activation, time between call and arrival of the Code Blue team, treatment details and outcome before and after the training process from January 2016 to December 2019. Chi-square test and logistic regression analysis were used to analyze the data., Results: A total of 139 Code Blue cases from the period of January 2016 to December 2019 were retrospectively studied. The wards where Code Blues occurred most frequently were the infectious diseases ward (n=31, 22.3%), the hematology and oncology ward (n=30, 21.6%), and the cardiology ward (n=15, 10.8%). Age, inpatient status, time of arrival, the time of cardiopulmonary resuscitation (CPR), and the cause of shock were all risk factors for death. After the training, the arrival time and recovery time were significantly reduced (P<0.01). The proportion of patients who were transferred to the ICU had increased (P<0.05), and the proportion of deaths had decreased (P<0.01). The survival curve improved (P<0.05)., Conclusions: It is very important to summarize the risk factors related to Code Blue. It is clear that the efficacy of the Code Blue events improved after training of the hospital staff in the Children's Hospital., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: Available at http://dx.doi.org/10.21037/tp-20-171). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

This paper investigates a distributed static and dynamic self-triggered impulsive control for nonlinear multiagent systems (MASs) where the impulsive gains follow a normal distribution, respectively. By integrating the distributed self-triggered control scheme with the impulsive control approach, a novel distributed impulsive controller is developed. The goal of the consensus of MASs can be realized using the proposed methods and several consensus criteria are obtained. Our schemes have some distinct superiorities, including the impulsive gains obeying a normal distribution, avoiding the continuous communication, and reducing the sampling frequency. Hence, compared with the existing literature, the conservativeness coming from the limitation of impulse gain and the sampling frequency is degraded, and it effectively extends the generality of the method in the practical application. Finally, the effectiveness of the theoretical results is demonstrated by two simulations.

Purpose: This study aimed to investigate the genetic aetiology in Chinese children diagnosed with status epilepticus (SE)., Methods: Next-generation sequencing, copy number variation (CNV) analysis, and other genetic testing methods were conducted for children with SE lacking an identifiable non-genetic aetiology. Furthermore, the phenotype and molecular data of patients with SE were retrospectively analysed., Results: Among children with SE lacking an identifiable non-genetic aetiology, 73 out of 163 children (44.8 %) were found to have causative variants associated with SE including 66 monogenic mutations in 22 genes and 7 CNVs. Based on the American College of Medical Genetics and Genomics scoring system, the monogenic variants included 64 pathogenic/likely pathogenic and 2 uncertain significance variants. SCN1A gene mutations (n = 32) were the most common cause, followed by TSC2 (n = 5), CACNA1A (n = 5), SCN2A (n = 4), SCN9A (n = 2) and DEPDC5 (n = 2) gene mutations. Sixteen mutations were identified in single genes. Furthermore, 51 (77.3 %) monogenic mutations were de novo. Age at SE onset < 1 year (odds ratio [OR] = 2.70, 95 % confidence interval [CI]: 1.25-5.83, p = 0.012) and co-morbidity of intellectual disability (OR = 3.36, 95 %CI: 1.61-6.99, p = 0.001) were independently associated with pathogenic genetic variants., Conclusion: This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

This article investigates the reliable output feedback control problem for networked nonlinear semi-Markov jump systems, in which a control strategy with redundant channels is established to reduce the adverse effect caused by packet dropouts. The actuator faults are fully considered in the setup. On the basis of stochastic analysis theory and fuzzy-model-based method, some criteria are established to guarantee the σ -error mean-square stability for the considered systems. As a consequence, the reliable output feedback controller design method is proposed, which can be utilized to deal with the actuator failures problem effectively. Finally, two illustrative examples are employed to explain the availability of the presented design approach, where the single-link robot arm system model is contained.

Background: The mortality prediction scores were widely used in pediatric intensive care units. However, their performances were unclear in Chinese patients and there were also no reports based on large sample sizes in China. This study aims to evaluate the performances of three existing severity assessment scores in predicting PICU mortality and to identify important determinants. Methods: This prospective observational cohort study was carried out in eight multidisciplinary, tertiary-care PICUs of teaching hospitals in China. All eligible patients admitted to the PICUs between Aug 1, 2016, and Jul 31, 2017, were consecutively enrolled, among whom 3,957 were included for analysis. We calculated PCIS, PRISM IV, and PELOD-2 scores based on patient data collected in the first 24 h after PICU admission. The in-hospital mortality was defined as all-cause death within 3 months after admission. The discrimination of mortality was assessed using the area under the receiver-operating characteristics curve (AUC) and calibrated using the Hosmer-Lemeshow goodness-of-fit test. Results: A total of 4,770 eligible patients were recruited (median age 18.2 months, overall mortality rate 4.7%, median length of PICU stay 6 days), and 3,957 participants were included in the analysis. The AUC (95% confidence intervals, CI) were 0.74 (0.71-0.78), 0.76 (0.73-0.80), and 0.80 (0.77-0.83) for PCIS, PRISM IV, and PELOD-2, respectively. The Hosmer-Lemeshow test gave a chi-square of 3.16 for PCIS, 2.16 for PRISM IV and 4.81 for PELOD-2 ( p ≥ 0.19). Cox regression identified five predictors from the items of scores better associated with higher death risk, with a C-index of 0.83 (95%CI 0.79-0.86), including higher platelet (HR = 1.85, 95% CI 1.59-2.16), invasive ventilation (HR = 1.40, 1.26-1.55), pupillary light reflex (HR = 1.31, 95% CI 1.22-1.42) scores, lower pH (HR 0.89, 0.84-0.94), and extreme PaO 2 (HR 2.60, 95% CI 1.61-4.19 for the 1st quantile vs. 4th quantile) scores. Conclusions: Performances of the three scores in predicting PICU mortality are comparable, and five predictors were identified with better prediction to PICU mortality in Chinese patients., (Copyright © 2020 Zhang, Huang, Wang, Li, Miao, Zhang, Pan, Zhang, Zhu, Chen, Li, Su, Bi, Chen, Jin, Miao, Kong, Cheng, Chen, Yan, Yan and Lu.)

Purpose: To describe the aetiology, clinical features, and short-term outcomes of children with status epilepticus (SE), in particular super-refractory SE (SRSE), by a nationwide multicentre study in China., Methods: In this retrospective study, inpatient children with SE were identified from neurology departments and paediatric intensive care units from 44 hospitals in 27 provinces of China between 2013 and 2015. Clinical data were exported from the Hospital Information System., Results: Clinical records from children with SE (n = 4255) aged 1 month to 18 years were enrolled; 13.1 % were diagnosed with SRSE. The most common known SE aetiology was acute symptomatic aetiology (42.8 %) and 50.2 % of SE was caused by epilepsy of unknown aetiology. Acute central nervous system (CNS) infections (38.8 %) were associated with SRSE (P < 0.001). The overall SE in-hospital mortality rate was 3.0 %, which was significantly higher in the children with SRSE than in those with non-SRSE (15.2 % versus 1.4 %, respectively; P < 0.001). Fourteen percent of the children with SE had various levels of neurological dysfunction at discharge. SRSE was a risk factor for in-hospital mortality (hazard ratio = 4.14; 95 % confidence interval [CI]: 2.34-7.32; P < 0.001) and neurological dysfunction at discharge (odds ratio = 2.85; 95 % CI: 1.90-4.27; P < 0.001)., Conclusion: Acute symptomatic aetiology was the most common known cause of paediatric SE. Aetiology was associated with progression to SRSE and short-term neurological dysfunction at discharge. Furthermore, SRSE was considered a risk factor for in-hospital mortality and short-term neurological dysfunction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Genetic diseases are a leading cause of death in infants in the intensive care setting; therefore, rapid and accurate genetic diagnosis is desired. To validate 24-h trio-exome sequencing (TES), samples from probands and their parents were processed by the AmpliSeq /Ion S5XL platform in a hospital clinical laboratory. Infants from the intensive care unit (ICU) suspected of having a genetic disease were enrolled. Regular and 24-h TES using the Agilent SureSelect capture kit/Illumina platform were performed on all samples in parallel. Of 33 enrolled infants, 23 received positive results with rapid TES, and an additional two diagnoses were achieved with regular TES. Among the 23 diagnosed patients, 10 experienced changes in medical management, such as hematopoietic stem cell transplant. Ten diagnosed cases were discharged prior to receiving the regular TES results; six received timely symptom control, and four withdrew medical support. Rapid TES enabled faster time to diagnosis, which resulted in an overall decrease in length of hospital stay. The 24-h TES can serve as a rapid response tool for patients with suspected monogenic disorders and can guide clinical decision-making in urgent cases., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Background: With the increasing use of carbapenems in clinic practice, carbapenem-resistant Enterobacteriaceae (CRE) has also increased, thus posing a significant threat to human health., Aim: To assess the effects of CRE colonization active screening and various CRE patient placements implemented in decreasing CRE infection risk., Methods: CRE colonization screening and various CRE patient placements were performed across CRE high-risk departments (PICU, NICU, neonatal wards and hematology departments) between 2017 and 2018, respectively., Finding: In 2018, more than 80% neonatal CRE positive patients were isolated using single room or same room isolation, and more than 50% non-neonatal patients were, with no cohort placement. The CRE nosocomial infection incidences decreased from 1.96% to 0.63% in NICU, and from 0.57% to 0.30% in neonatal wards (all P<0.05) while no significant changes were found in the other departments. The CRE colonization incidence at different length hospital stay (LOS) decreased at 8-14days and >14days LOS in CRE high-risk departments (all P<0.05). In addition, 62.5% clinical strains, 66.7% screening strains, and 74.1% nosocomial infection strains were belonged to CC17 complex group in neonatal isolates; while, 56.6%, 47.5% and 100% strains mentioned above were belonged to CC11 complex group in non-neonatal isolates respectively. The predominant carbapenemase gene was bla NDM-1 (98%) in neonatal and bla KPC-2 (70%) in non-neonatal CR-KP stains., Conclusions: Active CRE colonization surveillance and CRE positive patient propriety placement may decrease the CRE infection risk. Neonatal and non-neonatal CR-KP isolates showed different CRE molecular characteristics, which could further benefit CRE infection precaution and antibiotic therapy., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interests., (Copyright © 2020. Published by Elsevier Ltd.)

Background: A recent cluster of pneumonia cases in China was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the screening and diagnosis of corona virus disease 2019 (COVID-19) in our hospital., Methods: Developed a procedure for the identification of children cases with COVID-19 in outpatient and emergency department of our hospital, then we observed how this process works., Results: (I) There were 56 cases considered suspected cases, and 10 cases were confirmed as COVID-19. (II) Of the 10 confirmed COVID-19 cases admitted in our hospital, 5 were males and 5 were females, aged from 7 months to 11 years, the average age is 6.0±4.2 years, 6 cases were mild pneumonia, the others were upper respiratory tract infection. (III) We followed up 68 patients in isolation at home until symptoms disappeared. Non were missed in the patient's first visit. The sensitivity of this method is 100% and the specificity is 71.3%., Conclusions: Our screening process works well, and it is also necessary to establish a screening network in the hospital., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Accumulating evidence revealed that hypoxia contributed to many human diseases, including ischemic myocardium and heart failure (HF). In recent years, the roles of hypoxia in stem cell survival and cardiac biology have been studied extensively. However, the underlying molecular mechanisms remain to be elucidated. As a leading cause of HF, ischemic heart disease was correlated with hypoxia. In this study, we firstly constructed the hypoxia cell model by CoCl 2 in cardiac stem cells (CSCs) and found that hypoxia induced the cell proliferation and migration potential in CSCs. Then, we demonstrated that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was promoted in CoCl 2 -induced CSCs hypoxia model. Furthermore, we found that knockdown of MALAT1 inhibited the cell proliferation and migration in CoCl 2 -induced CSCs hypoxia model. In addition, we revealed that MALAT1 regulated the microRNA-155 (miR-155) expression in CSCs under both the normal and hypoxia conditions and further, manipulation of the miR-155 expression affected the role of MALAT1 in CoCl 2 -induced CSCs hypoxia cell model. We then illustrated that miR-155 regulated the myocyte enhancer factor 2A (MEF2A) expression in CSCs under both the normal and hypoxia conditions and further, changing the expression of MEF2A affected the role of miR-155. Finally, we demonstrated that MALAT1 regulated the MEF2A expression and exerted its role via modulation of the MALAT1/miR-155/MEF2A pathway. Taken together, our study illustrated that MALAT1 promoted the cell proliferation and migration in CoCl 2 -induced CSCs hypoxia model, acting mechanistically by promoting MEF2A expression via "sponging" miR-155., (© 2018 Wiley Periodicals, Inc.)

Bmi-1 gene is well recognized as an oncogene, but has been recently demonstrated to play a role in the self-renewal of tissue-specific stem cells. By using Bmi-1 GFP /+ mice, we investigated the role of Bmi-1 in cardiac stem/progenitor cells and myocardial repair. RT-PCR and flow cytometry analysis indicated that the expression of Bmi-1 was significantly higher in cardiac side population than the main population from CD45 - Ter119 - CD31 - heart cells. More Sca-1 + cardiac stem/progenitor cells were found in Bmi-1 GFP hi subpopulation, and these Bmi-1 GFP hi heart cells showed the potential of differentiation into SMM + smooth muscle-like cells and TnT + cardiomyocyte-like cells in vitro. The silencing of Bmi-1 significantly inhibited the proliferation and differentiation of heart cells. Otherwise, myocardial infarction induced a significantly increase (2.7-folds) of Bmi-1 GFP hi population, mainly within the infarction and border zones. These preliminary data suggest that Bmi-1 hi heart cells are enriched in cardiac stem/progenitor cells and may play a role in myocardial repair., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Endoplasmic reticulum (ER) stress has been suggested to play a role in the progression of plaque vulnerability and the occurrence of acute complications of coronary atherosclerosis. Atorvastatin is known to exert pleiotropic effects on the cardiovascular system. The present study aimed to examine the stabilizing effects of atorvastatin on vulnerable plaques within hyperhomocysteinemic apolipoprotein E‑deficient (ApoE‑/‑) mice, and to investigate the potential mechanisms underlying ER stress in ApoE‑/‑ mice and macrophages. In the present study, ApoE‑/‑ mice were administrated methionine or atorvastatin, and were sacrificed after 2 months. Necrotic core size, collagen content and inflammatory cytokine infiltration were subsequently measured in the aortic lesions, in order to investigate plaque stability. Treatment with atorvastatin decreased the number and size of necrotic cores, increased collagen content, and downregulated tumor necrosis factor (TNF)‑α and matrix metalloproteinase (MMP)‑9 mRNA expression, as compared with the methionine group. Immunohistochemical analysis indicated that atorvastatin administration prevented ER stress activation in aortic lesions of hyperhomocysteinemic mice. Furthermore, macrophages were challenged with homocysteine (Hcy) in the presence or absence of atorvastatin and thapsigargin (an ER stress inducer). Atorvastatin suppressed Hcy‑induced ER stress, and downregulated TNF‑α and MMP‑9 mRNA expression in the macrophages. Conversely, thapsigargin attenuated the inhibitory effects of atorvastatin against Hcy‑induced TNF‑α and MMP‑9 expression. These results indicated that hyperhomocysteinemia may promote atherosclerotic plaque development and instability. In addition, atorvastatin was able to improve atherosclerotic plaque stability in hyperhomocysteinemic mice by inhibiting ER stress.

A new method for CF3SO2Na-based direct trifluoromethylthiolation of C(sp(2))-H bonds has been developed. CF3SSCF3 is generated in situ from cheap and easy-to-handle CF3SO2Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using RfSO2Na., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To evaluate the diagnostic outcomes of magnetocardiography (MCG) on the patients with coronary artery disease and compared the outcomes between MCG, ECG and Echocardiography., Methods: MCG measurements were performed on 101 patients with coronary artery disease and 116 healthy volunteers with a seven-channel magnetocardiographic system (MCG7, SQUID AG, Germany) installed in an unshielded room. CAD was diagnosed when stenosis ≥ 70% in ≥ 1 vessel. Three quantitative indicators were analyzed, R-max/T-max ratio, R value and á average angle., Results: R-max/T-max ratio of CAD group (6.30 ± 4.07) was much higher than that of healthy group (3.73 ± 1.41) (P < 0.001), R value of CAD group (69.16 ± 27.87)% was significantly higher than that of healthy group (34.96 ± 19.09)% (P < 0.001), á average angle of CAD group (221.46° ± 64.53°) was higher than that of healthy group (24.32° ± 20.70°) (P < 0.01). In 75 of 101 CAD patients (74.26%), MCG had abnormal mapping patterns. The resting ECG examination showed ischemic changes, such as abnormal Q waves and ST-T change in 49 patients (48.51%). Echocardiography revealed abnormal left ventricular wall motion and asynergy in 46 patients (45.54%). Thus, the diagnostic outcomes of MCG for the patients with CAD were much significant than those of ECG and echocardiography (P < 0.001)., Conclusions: Our result showed that resting MCG under condition of an advanced data analysis has higher diagnostic outcomes and is superior to ECG or echocardiography for patients with CAD. MCG can detect ST-segment displacement caused by ischemic myocardium, thus helpful in diagnosing coronary artery disease early.

Objective: Neurogenic pulmonary edema (NPE ) was indicative of poor prognosis in the epidemic of enterovirus 71 infections. The pathogenesis of NPE remains poorly understood. The objectives of this experimental study were to explore whether RAS is activated during NPE in rabbit models induced by fibrin and the effects of an angiotensin converting enzyme inhibitor (enalaprilat) on NPE., Method: NPE models were induced by intracisternal injection of fibrinogen and thrombin. According to random number table method, 18 healthy adult New Zealand rabbits were assigned to three groups (with 6 in each) : normal control group (Con group), NPE group and enalaprilat treated (Ena) group. After establishment of NPE models, rabbits in Ena group were given intravenous enalaprilat 0.5 mg/kg. Expression of ACE,ACE2,AT1R mRNA of the lung tissue were evaluated by real-time polymerise chain reaction; and Ang II of the lung tissue was determined by enzyme linked immunosorbent assay ( ELISA ). Meanwhile, histopathological lung injury scores were evaluated., Result: ACE mRNA expression level in NPE group ( 17.2 ± 3.3) appeared an increasing trend in contrast to Con group ( 12.6 ± 5.2 ) and Ena group ( 11.5 ± 2.4, both P > 0.05 ). Compared with Con group (81 ± 22 ), ACE2 mRNA expression levels of NPE group ( 52 ± 6 ) and Ena group ( 45 ± 13 ) both decreased ( both P < 0.05 ) . ACE mRNA/ACE2 mRNA expression levels of NPE group ( 0.33 ± 0.06 ) and Ena group ( 0.26 ± 0.04 ) were higher than those of Con group ( 0.16 ± 0.05, both P < 0.05 ), as well as the ratio of Ena group decreased compared with untreated NPE group ( 0.26 ± 0.04 vs. 0.33 ± 0.06, P < 0.05 ) . There were no statistically significant differences in expression of AT1 mRNA of the lung tissue among three groups, but Ena group ( 4.8 ± 1.1) in contrast to NPE group ( 6.7 ± 1.3) has no significant difference (P > 0.05). Lung AngII level of NPE group [(540 ± 147) pg/ml] was significantly higher than that of Con group [(253 ± 37 ) pg/ml] and Ena group [(309 ± 35 ) pg/ml, both P < 0.05 ]. Gross pathologic examination showed that pink foamy edema fluid appeared in the tracheal tubes in NPE group, but spontaneously appeared in neither Con group nor Ena group; and the level of pulmonary subpleural bleeding in Con group, 12 graded 0; in NPE group, 2 graded II, 10 graded III; in Ena group, 2 graded, 8 grade II, 2 grade III. The histopathologic lung injury scores in Ena group was decreased in contrast to NPE group (1.36 ± 0.26 vs.2.32 ± 0.49, P < 0.05) and mainly for the improvement of alveolar overdistension and interstitial edema., Conclusion: The present study showed that when NPE occurs, a high lung AngII concentration was associated with an imbalance between ACE mRNA to ACE2 mRNA expression level. Activated local RAS in lung tissue resulted in lung injury. Enalaprilat treatment may attenuate lung injury by interventing local RAS in lung tissue with decreased ratio of ACE mRNA to ACE2 mRNA and lung AngII concentration. The result will be significant for the angiotensin converting enzyme inhibitor used in the theatment of NPE.

Objective: To evaluate efficacy of continuous blood purification (CBP) in childhood severe sepsis through the analysis of organ function, inflammatory mediators and prognosis., Method: Forty-seven children with severe sepsis aged 29 days -16 years who were treated in PICU of Shanghai and Zhejiang five hospitals during October 1, 2011 and September 30, 2012 were enrolled; 30 cases treated with CBP were recorded as logged group , 17 cases without CBP as unlogged group. Changes in the cardiovascular, respiratory function, renal function, inflammatory markers, PRISM score III, PCIS and survival were observed and compared between the two groups at baseline (d0), first days (d1), second days (d2), third days (d3), fifth days (d5)., Result: (1) Cardiovascular function: In d3 and d5, heart rate (HR) and mean arterial pressure (MAP) were improved as compared to unlogged group (121, 119 vs. 138, 137; 71, 80 mmHg vs. 63, 62 mmHg, P < 0.05), with no statistical significance in arterial blood lactate concentration. (2) Oxygenation index (PaO₂/FiO₂) and arterial oxygen saturation (SaO₂) increased as compared to unlogged group, but did not reach statistical significance. (3) Blood urea nitrogen (BUN) and creatinine (Cr) were improved as compared with unlogged group from d1 (P < 0.05). (4) Inflammatory mediators did not show significant differences. (5) Twenty-eight days survival rate: logged group was 70.0%, unlogged group was 52.9%, but the difference was not statistically significant (P = 0.242)., Conclusion: CBP can improve circulatory function, oxygenation, and renal function in children with severe sepsis. No evidence was found that CBP could decrease the level of inflammatory mediators, improve critical score and 28 days survival rate.

Objective: To learn application status of continuous blood purification (CBP) in pediatric intensive care unit (PICU), to provide reference to promote the development of CBP technology., Method: The survey of CBP application was conducted using questionnaire in 40 hospitals providing intensive care, which included children's hospitals and the pediatric sections of general hospitals from 28 provinces/municipalities/autonomous regions in China during March to July of 2012., Result: Totally 38 hospital replied, 25 hospitals carried out CBP technology, first carried out in 1997, the median year was 2008, 21 hospitals' PICU could independently carry out CBP device, 18 hospitals had the nurses who could professionally operate, routinely maintain the device. Continuous veno-venous hemodiafiltration was the largest implementation mode of CBP, accounting for 51.9%. Twenty-three hospitals used ordinary heparin, and 2 hospitals used low molecular weight heparin; 21 hospitals chose activated partial thromboplastin time as the coagulation testing, due to lack of equipment, only four hospitals chose activated clotting time as coagulation testing. Only 3 hospitals could apply before and after dilution joint technology. Kidney failure is still the disease accounting for the highest proportion of diseases requiring CBP application, accounting for 38.1%, followed by sepsis, 19.1%, drug poisoning 16.7%., Conclusion: CBP started 10 years ago, and got attention and promotion nearly five years ago in China, but the associated personnel, equipment were inadequate, anticoagulation, before and after dilution and other technical applications were not complete enough, high volume hemofiltration mode was seldom used.

Objective: To study the effect of thrombelastography (TEM) in the diagnosis of disseminated intravascular coagulation (DIC) in children., Method: The data of 117 children suffering from DIC in the pediatric intensive care unit (PICU) and Cardiologic ICU (CICU) in the authors' hospital from January 2010 to June 2012 were collected. Ninety-four children without DIC were enrolled into the control group. The platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimers and TEM were determined. The sensitivity and specificity of TEM were measured and the relevance of TEM and DIC was investigated to evaluate the effect of TEM and the conventional tests of the coagulation system in the diagnosis of DIC in children., Result: The average R reaction time in the DIC group was significantly longer than that in the control group[(13.3 ± 3.3)s vs. (4.5 ± 2.6)s, P = 0.000 5], and the average α-angle in the DIC group was smaller than that in the control group significantly (37.2° ± 1.4° vs. 55.6° ± 3.8°, P = 0.001 0). There was significant decrease in the maximal amplitude (MA) and amplitude (A) in the DIC group, compared with the control group. The OR value (95%CI) of the R reaction time,α-angle and MA was 3.538 (1.298-5.389), 2.472 (1.820-2.224) and 0.256 (0.263-0.831) respectively, which suggests good correlation with the existence of DIC (all P < 0.01). The specificity of R reaction time, α-angle and MA was higher than that of PT, APTT and D-dimers (85.7%, 73.5% and 72.9% vs. 27.0%, 42.1% and 68.2%) . The average R reaction time of children suffering from hemorrhage of severe liver disease(n = 36) was significantly longer than that of 40 healthy children [(9.2 ± 2.7) vs. (2.3 ± 1.8)s, P = 0.001 0], while the α-angle (42.8° ± 7.6° vs. 59.2° ± 10.8°, P = 0.040 0) and the MA value [(33.9 ± 5.1) vs.(56.0 ± 8.1) mm, P = 0.020 0] were significantly smaller. The average R reaction time of children suffering from congenital coagulopathy was significantly longer than that of healthy children [(6.8 ± 3.1) vs. (2.3 ± 1.8)s, P = 0.003 0], too., Conclusion: TEM, which has high specificity, is beneficial to the diagnosis of DIC in children.

The researches attempting to associate the PPARγ C161T polymorphism with coronary artery disease (CAD) yielded complicated and contradictory results. We aimed for more precise estimate of the relationship and conducted a comprehensive meta-analysis. Publications written in English or Chinese were screened in MEDLINE, Embase, CNKI, Wanfang and CBM. Data on 11 studies including 3,020 cases and 2,853 controls were extracted. A random-effects model was available to synthesize the inconsistent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias. The PPARγ C161T polymorphism followed Hard-Weinberg Equilibrium for all studies (P > 0.05).Overall, there was no evidence for a significant association under all genetic models but with distinct heterogeneity (T vs. C: P = 0.29, OR = 0.91, 95 %CI 0.77-1.08, P heterogeneity = 0.004, I (2) = 61.2 %). However, in the subgroup analysis by ethnicity, the T allele carriers showed a prominent 26 % risk reduction of CAD among Chinese (dominant genetic model: P = 0.03, 95 %CI 0.57-0.97, P heterogeneity = 0.03, I (2) = 56.1 %). After dividing into population source, the significance of CAD risk reduction was strengthened in hospital-based studies (allele comparison: P = 0.04, OR = 0.82, 95 %CI 0.67-1.00, P heterogeneity = 0.04, I (2) = 52.5 %; dominant model: P = 0.01, OR = 0.73, 95 %CI 0.57-0.92, P heterogeneity = 0.05, I (2) = 50.8 %). There was no obvious publication bias verified in the method of funnel plot and Egger's linear regression test (t = -0.11, P = 0.913). Taken together, our results revealed the PPARγ C161T polymorphism might play a moderate protective effect on developing CAD among Chinese, but not among Caucasians.

Purpose: Homocysteine (Hcy) has been shown to induce oxidative stress and apoptosis of endothelial progenitor cells (EPCs). AMP-activated protein kinase (AMPK) has been reported to have protective effects on endothelial function. However, effects of AMPK activation on Hcy-induced EPCs injury remain to be determined. In this study, we examined the effect of AMPK phosphorylation on Hcy-induced NO bioavailability impairment and NADPH oxidase 4 (Nox4) derived reactive oxygen species (ROS) accumulation in EPCs., Materials and Methods: EPCs were pre-treated with various concentrations of 5-amino-4-imidazolecarboxamide riboside-l-beta-D-ribofuranoside (AICAR), a pharmacological agonist of AMPK, and then incubated with Hcy for 24 h. Furthermore, we challenged EPCs with Hcy in the presence or absence of atorvastatin and AMPK-DN which expressed a dominant-negative mutant of AMPK. Migration, proliferation and apoptosis were assayed to evaluate EPCs function. NO production, expression of endothelial nitric oxide synthase (eNOS), intracellular ROS levels and Nox4 activation were determined to explore the potential mechanisms of Hcy-induced EPCs dysfunction., Results: We observed that AICAR attenuated the inhibition effects of Hcy on EPCs migration and proliferation. The apoptosis rates of EPCs were down-regulated by AICAR compared with the group treated with Hcy only [(0.25 mmol/L AICAR: 10.48 ± 1.6%; 0.5 mmol/L AICAR: 8.70 ± 1.0%; 1 mmol/L AICAR: 5.83 ± 1.3%) vs. (500 μmol/L Hcy only: 12.60 ± 1.9%)]. We also found that NO production and eNOS expression were up-regulated by AICAR compared with the group treated with Hcy only, while ROS accumulation and Nox4 activation were inhibited. Furthermore, atorvastatin suppressed Hcy-induced dysfunction of EPCs, increased NO production and eNOS expression, and down-regulated ROS accumulation and Nox4 activation. And these effects of atorvastatin could be blunted by AMPK-DN., Conclusion: AMPK activation inhibits eNOS down-regulation and Nox4-derived ROS accumulation induced by Hcy in EPCs, and may contribute to the protective effects of atorvastatin on endothelial function.