Identification of neurological complications in childhood influenza: a random forest model.

BACKGROUND: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1-2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). OBJECTIVE: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. METHODS: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. RESULTS: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. CONCLUSION: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.

Factors Associated with Severe Adenovirus Pneumonia in Children: A Retrospective Study from Guangzhou, China (2017-2019).

BACKGROUND Adenovirus infections are prevalent in children, typically presenting with mild or asymptomatic symptoms. However, some children develop severe pneumonia necessitating hospitalization. This retrospective study aimed to identify risk factors associated with severe adenovirus pneumonia in children. MATERIAL AND METHODS We screened consecutive children admitted for community-acquired pneumonia at the Emergency Department of Guangzhou Women's and Children's Medical Center between 2017 and 2019. Adenovirus infection was confirmed through rapid respiratory virus assay, RT-PCR assay from respiratory secretions, or serum IgM antibodies. According to Chinese guidelines, patients with pneumonia were classified into severe and mild groups. We assessed risk factors for severe adenovirus pneumonia by comparing clinical features and laboratory indicators, then included differing factors between the 2 groups in a logistic regression analysis. Data analysis was performed using SPSS 26.0 software. RESULTS Our study included 173 children diagnosed with adenovirus pneumonia (117 severe, 56 mild). The median age was 40 months, with 64 male patients. Univariate analysis and binary logistic regression analysis revealed that pleural effusion (13.449 [1.226-147.510], p=0.033), electrolyte disturbances (15.149 [2.724-84.246], p=0.002), oxygen therapy (258.219 [20.684-3223.548], p<0.001), bronchoscopy (26.781 [6.088-117.805], p<0.001), and steroid administration (6.584 [1.497-28.953], p=0.013) were associated with the severity of adenovirus pneumonia. CONCLUSIONS This single-center retrospective study identified pleural effusion, the need for bronchoscopy, oxygen therapy, and steroid treatment, along with impaired serum electrolytes, as factors associated with severe adenovirus pneumonia in children.

Clinical evaluation of acute necrotizing encephalopathy in children.

Objective: Acute necrotizing encephalopathy (ANE) is a rare but severe encephalopathy and is associated with a high morbidity and mortality. We aimed to analyze and compare the clinical features and predictive indicators of pediatric ANE. Materials and methods: This retrospective study included children with ANE diagnosed at Guangzhou Women and Children's Medical Center between November 2018 and January 2020. Pediatric patients' information, including clinical characteristics, laboratory tests, neuroelectrophysiology and brain magnetic resonance imaging (MRI) findings, MRI score, brainstem auditory evoked potential (BAEP) grades, ANE severity scores (ANE-SS), and modified Rankin scale (mRS), were collected. Results: Twelve ANE patients were included. Among them, one patient (8.3%) died from brainstem dysfunction, one (8.3%) recovered and 10 (83.3%) experienced neurological sequelae. All patients had an initial viral infection and neurological symptoms such as acute disturbance of consciousness (ADOC) or seizure, and the interval from onset of the disease to neurological manifestations was 3 (1.25-3) days. MRI score-I ranged from 1 to 3 (1.8 ± 0.7), MRI score-II ranged from 1 to 4 (2.5 ± 1.1). ANE-SS varied from 1 to 6 (3.9 ± 1.3). The scores of mRS were from 0 to 6 (2.9 ± 1.7). Higher MRI score were associated with worse outcomes, while the BAEP grade and ANE-SS score were not significantly associated with mRS. Conclusion: ANE is a severe encephalopathy syndrome with rapid progression, resulting in serious neurological sequelae. Compared with BAEP grade and ANE-SS, brain MRI shows more comprehensive advantages in predicting the prognosis of ANE patients. More in-depth research and better indicators are still needed to support the evaluation and treatment of ANE.

Enterovirus 71 VP1 promotes 5-HT release by upregulating the expression of ERICH3 and methyltransferase ZC3H13.

BACKGROUND AND AIM: The effect of structural viral protein 1 (VP1) on neurological damage caused by enterovirus 71 (EV71) infection is unclear. This study aimed to explore the transcriptome changes in EV infected patients and the role of VP1 on the cell secretion pathway of neuron cells. METHODS: In our cohort, EV infected patients were enrolled, and RNA-seq analysis was used to evaluate the distinct transcript patterns of cerebrospinal fluid (CSF). The EV71 VP1-overexpressing vector (pEGFP-c3-VP1) was generated and transfected into neuron cells. The relationship between Glutamate Rich 3 (ERICH3) and methyltransferase Zinc Finger CCCH-Type Containing 13 (ZC3H13) and their effect on the serotonin (5-HT) release of neuron cells were explored using small interfering RNA. The expression of ERICH3 and ZC3H13 and concentration of 5-HT were determined using real-time PCR, Western blot, and ELISA, respectively. RESULT: The expression of ERICH3 and ZC3H13 were significantly upregulated in EV infected patients with neurological symptoms compared to those without (P < 0.05). The ERICH3 gene had many N6-methyladenosine (m6A) binding sites that can be regulated by m6A modification. Further, the expression of ERICH3 and ZC3H13 were elevated significantly in EV71-VP1 overexpressing neuron cells (P < 0.05). Moreover, ERICH3 or ZC3H13 deficiency could significantly downregulate the release of 5-HT in VP1-overexpressing cells (P < 0.05). Nonetheless, ERICH3 expression was significantly suppressed when ZC3H13 was silenced in neuron cells and vice versa (P < 0.05). CONCLUSIONS: EV71-VP1 can promote 5-HT release by upregulating the expression of ERICH3 and ZC3H13. 5-HT might be a novel therapeutic target for EV71 infection-induced fatal neuronal damage.

Characterization of Enterovirus Associated m6A RNA Methylation in Children With Neurological Symptoms: A Prospective Cohort Study.

Little is known about the particular changes of N6-methyladenosine (m6A) RNA methylation in enterovirus (EV) infection among children with neurologic symptoms. Here, we determined the characterization of EV associated m6A RNA methylation in this population. A prospective cohort study was conducted from 2018/2 to 2019/12 at the Guangzhou Women and Children's Medical Center. We included EV infected children with and without neurological symptoms. High-throughput m(6)A-RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis were used to evaluate the m6A RNA methylation and transcript expression of cerebrospinal fluid samples. The functional annotation and pathways of differentially methylated m6A genes with synchronously differential expression were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Seven patients were enrolled in the control group, and 13 cases were in the neurological symptoms (NS) group. A total of 3472 differentially expressed genes and 957 m6A modified genes were identified. A conjoint analysis of MeRIP-seq and RNA-seq data found 1064 genes with significant changes in both the m6A modifications and mRNA levels. The different m6A RNA methylation was increased in the transcriptome's CDS regions but decreased in both the 3'UTRs and stop codon among the NS group. Functional annotation like the "oxidative phosphorylation" gene pathway, "Parkinson's disease" and GO terms like "respiratory electron transport chain," "cellular metabolic process," and "oxidation-reduction process" was enriched in symptomatic patients. Our study elucidated the changes of RNA m6A methylation patterns and related cellular functions and signaling pathways in EV patients with neurologic symptoms.

[Relationship between IKZF3 Gene Single Nucleotide Polymorphisms and Childhood Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of IKAROS family Zinc finger 3 (IKZF3) gene and the risk of acute lymphoblastic leukemia (ALL) in children. METHODS: The peripheral blood samples from 286 children with ALL and 382 healthy children were collected and divided into ALL group and control group, respectively. The genotypes of IKZF3 gene at rs62066988 C > T and rs12946510 C > T were detected by quantitative PCR with TaqMan detection system, and their correlation with ALL was analyzed. RESULTS: The distribution frequencies of CC, CT and TT genotypes at rs62066988 in ALL group were 58.39%, 37.06% and 4.55%, respectively, while those in control group were 69.19%, 27.68% and 3.13%, respectively. The distribution frequencies of CC, CT and TT genotypes at rs12946510 in ALL group were 58.16%, 34.75% and 7.09%, respectively, while those in control group were 55.76%, 37.43% and 6.81%, respectively. Compared with the control group, the distribution frequency of CT/TT genotype at rs62066988 was significantly increased in the ALL group (OR=1.59, 95%CI: 1.16-2.19, P=0.004). However, there was no significant difference in the distribution of rs12946510 C > T polymorphism between ALL group and control group. CONCLUSION: The CT/TT genotype of IKZF3 at the site of rs62066988 is associated with the increased risk of ALL in children.

Parameters Indicating Development of Influenza-Associated Acute Necrotizing Encephalopathy: Experiences from a Single Center.

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.

Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy in Children: A Retrospective Single-Center Study.

BACKGROUND Although influenza primarily affects the respiratory system, it can cause severe neurological complications, especially in younger children, but knowledge about the early indicators of acute necrotizing encephalopathy (ANE) is limited. The main purpose of this article is to summarize the clinical characteristics, diagnosis, and treatment of neurological complications of influenza in children, and to identify factors associated with ANE. MATERIAL AND METHODS This was a retrospective study of children with confirmed influenza with neurological complications treated between 01/2014 and 12/2019 at Guangzhou Women and Children's Medical Center. A receiver operating characteristics curve analysis was performed to determine the prognostic value of selected variables. RESULTS Sixty-three children with IAE (n=33) and ANE (n=30) were included. Compared with the IAE group, the ANE group showed higher proportions of fever and acute disturbance of consciousness, higher alanine aminotransferase, higher aspartate aminotransferase, higher creatinine kinase, higher procalcitonin, higher cerebrospinal fluid (CSF) protein, and lower CSF white blood cells (all P<0.05). The areas under the curve (AUCs) for procalcitonin and CSF proteins, used to differentiate IAE and ANE, were 0.790 and 0.736, respectively. The sensitivity and specificity of PCT >4.25 ng/ml to predict ANE were 73.3% and 100.0%, respectively. The sensitivity and specificity of CSF protein >0.48 g/L to predict ANE were 76.7% and 69.7%, respectively. Thirteen (43.3%) children with ANE and none with IAE died (P<0.0001). CONCLUSIONS High levels of CSF protein and serum procalcitonin might be used as early indicators for ANE. All children admitted with neurological findings, especially during the influenza season, should be evaluated for influenza-related neurological complications.

Effect of Maillard reaction conditions on the solubility and molecular properties of wheat gluten-maltose conjugates.

In this experiment, the conjugation reaction between gluten and maltose via Maillard reaction under dry-heated condition was studied. The process conditions for the preparation of protein-maltose conjugates with optimum solubility were optimized by using Box-Behnken model. The conjugation reaction and the structure changes of the protein-maltose conjugates were confirmed by infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The results showed that the process conditions for the preparation of protein-maltose conjugates with optimum solubility were as follows: temperature 50.72°C, time 1.92 days, and gluten/maltose (W/W) 267.36%. The infrared spectroscopy showed that the structure of the modified protein had a very obvious change, including the decrease in ß-fold and ß-turn and the increase in α-helix at a certain degree. But the conjugation reaction has little effect on the irregular coiled structure. The scanning electron microscopy showed that the microstructure of gluten is small grainy, but gluten-maltose conjugate looks sheet with bigger volume.

Characteristics of Nosocomial Infections in Children Screened for SARS-CoV-2 Infection in China.

BACKGROUND This study summarizes the characteristics of children screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reports the case of 1 child who was diagnosed with SARS-CoV-2 infection in Guangzhou Women and Children's Medical Center and the cases of his family members. MATERIAL AND METHODS The medical records of 159 children who were admitted to our hospital from January 23 to March 20, 2020, were retrospectively analyzed. Samples from pharyngeal or/and anal swabs were subjected to reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 within 12 h of patient admission; a second RT-PCR test was done 24 h after the first test. RESULTS Of the 159 patients, 151 patients had epidemiological histories, 14 patients had cluster onset, and 8 patients had no epidemiological history but had symptoms similar to coronavirus disease 2019 (COVID-19). The most common symptom was fever (n=125), followed by respiratory and gastrointestinal symptoms. A 7-year-old boy in a cluster family from Wuhan was confirmed with asymptomatic SARS-CoV-2 infection with ground-glass opacity shadows on his lung computed tomography scan, and his swab RT-PCR test had not turned negative until day 19 of his hospitalization. In patients who did not test positive for SARS-CoV-2, influenza, respiratory syncytial virus, and adenovirus were observed. A total of 158 patients recovered, were discharged, and experienced no abnormalities during follow-up. CONCLUSIONS For SARS-CoV-2 nosocomial infections, taking a "standard prevention & contact isolation & droplet isolation & air isolation" strategy can prevent infection effectively. Children with clustered disease need close monitoring.

Biochemical, sensory and microbiological attributes of bream (Megalobrama amblycephala) during partial freezing and chilled storage.

BACKGROUND: Bream is one of the main farmed freshwater fish species in China. This study aimed to examine the nucleotide degradation of bream during partial freezing and chilled storage and to assess the possible usefulness of nucleotide ratios (K, Ki, H, P, Fr and G values) as freshness indices in comparison with sensory assessment and total viable counts. RESULTS: Total viable counts were 5.74 and 4.66 log(colony-forming units g(-1)) on the day of sensory rejection under chilled storage and partial freezing storage respectively. The inosine 5-monophosphate decrease and inosine increase were faster in chilled storage than in partial freezing storage. Hypoxanthine levels increased continuously with time under both storage regimes. Among the nucleotide ratios, the K, Ki, P, G and Fr values were superior to the H value and provided useful freshness indicators for both storage conditions. CONCLUSION: Bream in chilled storage were sensorially acceptable only up to 10 days, compared with 33 days for bream in partial freezing storage. Partial freezing delayed the nucleotide degradation of bream.

[Expression and significance of integrins subunits in laryngeal squamous cell carcinoma].

OBJECTIVE: This study was to investigate the expression and significance of Integrins subunits in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression of Integrins subunits was detected by cDNA microarray in 4 cases of primary LSCC tissues and corresponding adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) were used to identify the different expression of Integrins subunits in 24 cases of primary LSCC tissues and corresponding adjacent normal tissues. RESULT: A cDNA microarray analysis revealed significant changes in the expression of Integrins subunits, with IntegrinalphaV, Integrinbeta8 being up-regulated and Integrinalpha8 being down-regulated. The result of RT-PCR was consistent with that of cDNA microarray. The mRNA levels of IntegrinalphaV and Integrinbeta8 were significantly higher in LSCC tissues than that in corresponding adjacent normal tissues (1.0131 +/- 0.4780 vs 0.7591 +/- 0.4678 for IntegrinalphaV, P<0.05, 1.7362 +/- 1.3849 vs 1.2267 +/- 0.9363 for Integrinbeta8, P<0.05). The mRNA levels of Integrinalpha8 were significantly lower in LSCC tissues than that in corresponding adjacent normal tissues (0.2646 +/- 0.2622 vs 0.5457 +/- 0.3827, P<0.05). CONCLUSION: The expression of IntegrinalphaV, Integrinbeta8, Integrinalpha8 were significantly up-regulated or down-regulated in laryngeal squamous cell carcinoma, which may relate to tumorigenesis and development of laryngeal squamous cell carcinoma.

Text mining biomedical literature for constructing gene regulatory networks.

In this paper, we present the framework of a Gene Regulatory Networks System: GRNS. The goals of GRNS include automatically mining biomedical literature to extract gene regulatory information (strain number, genotype, gene regulatory relation, and phenotype), automatically constructing gene regulatory networks based on extracted information and integrating biomedical knowledge into the regulatory networks.