Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. DATA SOURCES: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". RESULTS: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. CONCLUSIONS: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

Intramedullary Nailing Versus Open Reduction and Plate Fixation for Lateral Malleolar Fractures: A Meta-Analysis.

The fixation for lateral malleolar fracture in ankle fractures is still controversial. The purpose of this meta-analysis is to compare clinical and radiological outcomes between intramedullary nail (IMN) and plate for lateral malleolar fractures in ankle fractures. The PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCTs) from databases inception to June 2023. Data on outcomes were extracted and the methodological quality of the included studies were assessed. A meta-analysis was performed using RevMan 5.3 software when the data extracted from included studies could be synthesized. Seven RCTs were included. The methodological quality of the included studies was moderate to high. The meta-analysis results showed that the infection rate of the IMN group was significantly lower than that of the plate group (RR = 0.38; 95%CI 0.18-0.82; p = .01). There were no significant differences between the 2 groups in Olerud and Molander Ankle Score (OMAS), union rate, radiological outcomes, nerve injury rate, reoperation rate, loss of reduction, and total complication rate. Our present meta-analysis demonstrated that the IMN might be a better method for the fixation of lateral malleolar fracture in ankle fracture, as the infection rate was significantly lower than a plate.

Strengthen the purification of eutrophic water and improve the characteristics of sediment by functional ecological floating bed suspended calcium peroxide and sponge iron jointly.

To overcome the shortcomings of conventional ecological floating bed (CEFB) in purifying landscape water, this study constructed a functional ecological floating bed (FEFB) through the suspension of calcium peroxide (CP) and sponge iron (SI) jointly below the CEFB. The purification effect of water quality and influence of sediment were compared in control check, CEFB, and FEFB systems, which were loaded the same sediment and reclaimed water in a field experiment. Results showed that the FEFB suspended with CP and SI had evident purification effect on the quality of landscape water supplied with reclaimed water and can maintain stably the nutrient status of the water body at mesotrophic levels and low turbidity. The FEFB promoted the degradation of humus, thus eliminating the chroma risk in water body caused by the decay of plants from the CEFB. Moreover, the FEFB can control the sediment mass produced, reduce the total nitrogen (TN) mass of sediment, and decrease the transformable TN (TTN) content in the sediment. The FEFB enhanced the stability of phosphorus (P) in the sediment, where the relative content of Ca-P and stable P reached 42.18% and 64.27%, respectively. To sum up, the FEFB suspended with SI and CP can not only effectively control the eutrophication and sensory index of landscape water but also change the TTN content and P forms in sediment, making the sediment more stable. Thus, the FEFB provides an innovative approach to reduce endogenous nutrient release for landscape water along with recharging with reclaimed water.

Response mechanism of microorganisms to the inhibition of endogenous pollution release by calcium peroxide.

To further explore the response mechanism of microorganisms to the synchronous control of nitrogen and phosphorus release from sediments by CaO2, the spatiotemporal changes in the physical, chemical and biological indicators of the overlying water, interstitial water and sediments in each reactor were measured in the experiment. The experiment results showed that CaO2 could increase the ammonia monooxygenase activity, nitrite oxidase activity and Nitrospira abundance in the sediment near its dosing position, and enhanced the activities of nitrate reductase and nitrite reductase at a certain distance from the dosing position, thereby promoting nitrogen removal in sediments through the alternating process of nitrification and denitrification. At the same time, the increase of alkaline phosphatase activity and Saccharimonadales abundance in the test groups accelerated the hydrolysis of organic phosphorus, and the P immobilization in sediments was realized through the subsequent precipitation reaction of Ca2+ and PO43- under alkaline conditions. In addition, the enhanced activities of dehydrogenase and catalase ensured that CaO2 would not cause great killing effect on microorganisms when improving the hypoxic conditions and inhibiting endogenous release. As a result, the dissolved product of CaO2 such as Ca(OH)2 and H2O2 reduced the nutrients concentration and killed the algae, which kept the algae density and chlorophyll a concentration at a low level throughout the test groups. Therefore, this study systematically clarified the microbial mechanism of CaO2 synchronously controlling the release of nitrogen and phosphorus from sediments, which provided a new idea for the remediation of endogenous pollution in the water system.

DeepSE: Detecting super-enhancers among typical enhancers using only sequence feature embeddings.

Super-enhancer (SE) is a cluster of active typical enhancers (TE) with high levels of the Mediator complex, master transcriptional factors, and chromatin regulators. SEs play a key role in the control of cell identity and disease. Traditionally, scientists used a variety of high-throughput data of different transcriptional factors or chromatin marks to distinguish SEs from TEs. This kind of experimental methods are usually costly and time-consuming. In this paper, we proposed a model DeepSE, which is based on a deep convolutional neural network model, to distinguish the SEs from TEs. DeepSE represent the DNA sequences using the dna2vec feature embeddings. With only the DNA sequence information, DeepSE outperformed all state-of-the-art methods. In addition, DeepSE can be generalized well across different cell lines, which implied that cell-type specific SEs may share hidden sequence patterns across different cell lines. The source code and data are stored in GitHub (https://github.com/QiaoyingJi/DeepSE).

[Application of the artificial intelligence-rapid whole-genome sequencing diagnostic system in the neonatal/pediatric intensive care unit].

Pediatric patients in the neonatal intensive care unit (NICU) and the pediatric intensive care unit (PICU) have a high incidence rate of genetic diseases, and early rapid etiological diagnosis and targeted interventions can help to reduce mortality or improve prognosis. Whole-genome sequencing covers more comprehensive information including point mutation, copy number, and structural and rearrangement variations in the intron region and has become one of the powerful diagnostic tools for genetic diseases. Sequencing data require highly professional judgment and interpretation and are returned for clinical application after several weeks, which cannot meet the need for the diagnosis and treatment of genetic diseases in children. This article introduces the clinical application of rapid whole-genome sequencing in the NICU/PICU and briefly describes related techniques of artificial intelligence-rapid whole-genome sequencing diagnostic system, a rapid high-throughput automated platform for the diagnosis of genetic diseases. The diagnostic system introduces artificial intelligence into the processing of data after whole-genome sequencing and can solve the problems of long time and professional interpretation required for routine genome sequencing and provide a rapid diagnostic regimen for critically ill children suspected of genetic diseases within 24 hours, and therefore, it holds promise for clinical application.

Impact of smoking status and cumulative smoking exposure on tumor recurrence of non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate the effect of smoking status, cumulative smoking exposure and smoking cessation on the outcomes of patient with non-muscle-invasive bladder cancer (NMIBC). METHODS: We collected smoking data from 484 patients with NMIBC who were treated with transurethral resection (TUR); smoking status was categorized as (never smokers vs current smokers vs former smokers). Cumulative smoking exposure was categorized as high smoking exposure (cigarette index ≥400) versus low smoking exposure (cigarette index <400). Association with outcomes was examined by multivariable analyses after adjusting for the effects of standard clinicopathologic factors, and the Kaplan-Meier method was used to estimate the effect of smoking status and cumulative smoking exposure on RFS. RESULTS: A total of 168 (34.7 %) patients were never smoker, 121 (25 %) patients were current smokers, and 195 (40.3 %) patients were former smokers. The median follow-up was 25 months. By multivariate analysis, pathological grade (p = 0.013), history of recurrence (p < 0.001), number of tumors (p < 0.001) and size of tumors (p = 0.013) were significantly associated with tumor recurrence; nevertheless, smoking status did not influence tumor recurrence (p = 0.063). Among current and former smokers, cumulative smoking exposure was significantly associated with tumor recurrence (p < 0.001), compared to current smokers, patients with smoking cessation ≥10 years had a lower risk of tumor recurrence [hazard ratio (HR) 0.456, p = 0.007]. CONCLUSIONS: Smoking affects the prognosis of patient with NMIBC, which is still controversial; however, among ever smokers, a high cumulative exposure smoking can significantly increase the risk of tumor recurrence. Quitting smoking might be associated with a lower recurrence rate for patients with NMIBC.

A highly malignant case of neuroblastoma with substantial increase of single-nucleotide variants and normal mismatch repair system: A case report.

RATIONALE: Neuroblastoma is a common abdominal malignancy in children. The chemoresistant and relapsed cases have poor prognosis. The genetic background and the mechanism of resistance remain unelucidated. Next-generation sequence (NGS) is becoming a popular tool to unravel the genetic background and to guide precision medicine in oncology studies as well as in clinical practice. PATIENT CONCERNS: Here we report a neuroblastoma case of a boy aged 2 years and 8 months when first diagnosed, with multiple metastatic sites found in both lungs. The metastatic tumors were resistant to chemotherapy and the patient suffered from severe bone marrow suppression. NGS of the whole exon revealed somatic mutations including 9666 single-nucleotide variants (SNVs) from 5148 genes, 55 copy number variations (CNVs), and 140 insertion-deletion variations. The high frequency of SNVs makes it distinguished case. However, no mutation of key tumor driver genes with functional significance was identified. No abnormality was found in nucleic acid synthesis enzymes. No amplification of c-Myc and n-Myc was found by fluorescence in situ hybridization (FISH). Both NGS and immunohistochemistry (IHC) analysis indicated that DNA mismatch repair (MMR) system was intact. INTERVENTIONS: After initial diagnosis, the patient received combinational chemotherapy, which includes vindesine, an analogue of adriamycin suggested by NGS data, for 4 months. Radical section of the tumor together with the left kidney and the left adrenal gland was performed 5 months after diagnosis. Postsurgical chemotherapy protocols was similar with the previous. OUTCOMES: The patient died 2 years after initial diagnosis after 8 relapses following combinational chemotherapy. LESSONS: This case of neuroblastoma is with pronounced somatic mutations but unidentified driver gene and therapeutic target. Although NGS is a potentially powerful tool to guide precision medicine, at current stage, its application in the clinic certainly has its limits. The underlying mechanism of the substantially increased SNV number, as well as the malignant behaviors of the tumor, is yet to be revealed.

[Structuralization of digestive endoscopy report based on NLP].

This paper presents a method based on NLP to realize structuralization of digestive endoscopy reports. The method is taking advantage of existing NLP's processing technologies and introducing minimal standard terminology (MST) to transform a narrative gastroscopy report into the structuralization report based on MST, whose accuracy rate is 92.3%.

[Design and practice of the Clinical Information System for ICU].

This paper presents a typical Clinical Information System for ICU and its design and implementation. This system is able to capture and archive vital data from the monitor network, providing a whole digital solution in ICU. These vital data can be used in quantitative analysis in the computer-assisted decision support.