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Abstract Background To understand the clinical characteristics and prognosis of respiratory syncytial virus (RSV)-related encephalopathy in children. Methods A retrospective analysis of the data of children who were diagnosed with RSV-related encephalopathy and admitted to the paediatric intensive care unit (PICU) of Beijing Children’s Hospital between November 2016 and November 2023 was performed. Results Four hundred and sixty-four children with RSV infection were treated in the PICU, and eight of these patients (1.7%) were diagnosed with RSV-related encephalopathy. The mean age of the patients was 24.89 (5.92 ∼ 36.86) months. Two patients had underlying diseases. The time from the onset of illness to impaired consciousness was 3 (1.88–3.75) days. Five patients had convulsions, and three patients had an epileptic status. The serum procalcitonin (PCT) level was 1.63 (0.24, 39.85) ng/ml for the eight patients, and the cerebrospinal fluid (CSF) protein level was 232 (163 ∼ 848) g/L. Among the 8 patients, four patients underwent electroencephalogram (EEG) monitoring or examination. One patient showed continuous low-voltage, nonresponsive activity, and another patient displayed persistent slow waves, the remaining two patients had negative results. One patient had a combination of acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Additionally, one patient had ANE, and another had acute brain swelling (ABS). One patient died in the hospital, and the other seven patients were discharged with improvement. Routine follow-up was conducted for 4.58(0.5 ∼ 6.50) years, and all patients fully recovered. Conclusions RSV-related encephalopathy could have varying clinical manifestations, and some types, such as ANE and ABS, are dangerous and can lead to death.

Abstract Background Ligilactobacillus salivarius has been frequently isolated from the gut microbiota of humans and domesticated animals and has been studied as a candidate probiotic. Badger (Meles meles) is known as a “generalist” species that consumes complex foods and exhibits tolerance and resistance to certain pathogens, which can be partly attributed to the beneficial microbes such as L. salivarius in the gut microbiota. However, our understanding of the beneficial traits and genomic features of badger-originated L. salivarius remains elusive. Results In this study, nine L. salivarius strains were isolated from wild badgers' feces, one of which exhibited good probiotic properties. Complete genomes of the nine L. salivarius strains were generated, and comparative genomic analysis was performed with the publicly available complete genomes of L. salivarius obtained from humans and domesticated animals. The strains originating from badgers harbored a larger genome, a higher number of protein-coding sequences, and functionally annotated genes than those originating from humans and chickens. The pan-genome phylogenetic tree demonstrated that the strains originating from badgers formed a separate clade, and totally 412 gene families (12.6% of the total gene families in the pan-genome) were identified as genes gained by the last common ancestor of the badger group. The badger group harbored significantly more gene families responsible for the degradation of complex carbohydrate substrates and production of polysaccharides than strains from other hosts; many of these were acquired by gene gain events. Conclusions A candidate probiotic and nine L. salivarius complete genomes were obtained from the badgers’ gut microbiome, and several beneficial genes were identified to be specifically present in the badger-originated strains that were gained in the evolution. Our study provides novel insights into the adaptation of L. salivarius to the intestinal habitat of wild badgers and provides valuable strain and genome resources for the development of L. salivarius as a probiotic.

Abstract Background Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. Methods This was a retrospective cohort study using the South Korea National Health Insurance database (2014–2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months’ data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). Results Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75–0.78); mean PPPY total healthcare costs were 2093 USD. Conclusions Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Abstract Background Salmonella Derby is one of the most predominant Salmonella serotypes that seriously threatens food safety. This bacterium can be further differentiated to sub-populations with different population sizes; however, whether and how the S. Derby–gut microbiota interactions affect epidemic patterns of S. Derby sub-populations remain largely unknown. Results We selected two representative strains, 14T and 14C, which represent rarely distributed and prevalent sub-populations of the S. Derby ST40 group, respectively, to address this question using a mouse model. Effects of oral administration of both strains was monitored for 14 days. Alpha diversity of gut microbiota at early stages of infection (4 h post infection) was higher in 14C-treated mice and lower in 14T-treated mice compared with controls. Strain 14T triggered stronger inflammation responses but with lower pathogen titer in spleen compared with strain 14C at 14 days post infection. Certain known probiotic bacteria that can hinder colonization of Salmonella, such as Bifidobacteriaceae and Akkermansiaceae, exhibited increased relative abundance in 14T-treated mice compared with 14C-treated mice. Our results also demonstrated that Ligilactobacillus strains isolated from gut microbiota showed stronger antagonistic activity against strain 14T compared with strain 14C. Conclusions We identified how S. Derby infection affected gut microbiota composition, and found that the 14T strain, which represented a rarely distributed S. Derby sub-population, triggered stronger host inflammation responses and gut microbiota disturbance compared with the 14C strain, which represented a prevalent S. Derby sub-population. This study provides novel insights on the impacts of gut microbiota on the epidemic patterns of Salmonella populations.

Abstract Background Cerebral-cardiac syndrome, newly developed cardiac damage manifestations subsequent to cerebral injuries, is a common complication of stroke and leads to increased morbidity and mortality. The current study is aimed to develop a risk prediction scale to stratify high-risk population of CCS among ischemic stroke patients. Methods The study included 410 cases from four tertiary medical centers from June 2018 to April 2019. The risk prediction model was established via logistic regression from the derivation cohort including 250 cases admitted between June 2018 and December 2018. Another 160 cases admitted from January 2019 to April 2019 were included as the validation cohort for external validation. The performance of the model was determined by the area under curve of the receiver operating characteristic curve. A rating scale was developed based on the magnitude of the logistic regression coefficient. Results The prevalence of CCS was 55.2% in our study. The predictive model derived from the derivation cohort showed good calibration by Hosmer-Lemeshow test (P = 0.492), and showed sensitivity of 0.935, specificity of 0.720, and Youden index of 0.655. The C-statistic for derivation and validation cohort were 0.888 and 0.813, respectively. Our PANSCAN score (0 to 10 points) was then established, which consists of the following independent risk factors: PT(12 s–14 s = 0; otherwise = 1), APTT(30s–45s = 0, otherwise = 1), Neutrophils(50–70% = 0; otherwise = 1), Sex(female = 1), Carotid artery stenosis(normal or mild = 0; moderate to severe = 2), Age(≥65 years = 1), NIHSS score(1 to 4 = 2; ≥5 = 3). Patients scored 3 or more points were stratified as high risk. Conclusion The risk prediction model showed satisfactory prediction effects. The PANSCAN scale provides convenient reference for preventative treatment and early management for high-risk patients. Trial registration The study was retrospectively registered in Chinese Trial Registry. The date of registration is April 17, 2019. Trial registration number: ChiCTR1900022587 .

Abstract Background Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. Methods We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(−)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. Results After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. Conclusions The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

Abstract Background Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) near chromosome 9p21 have been associated with both atherosclerosis and artery calcification, but the underlying mechanisms remained largely unknown. Considering that CDKN2A/2B is a frequently reported site for DNA methylation, this study aimed to evaluate whether carotid artery calcification (CarAC) is related to methylation levels of CDKN2A/2B in patients with ischemic stroke. Methods DNA methylation levels of CDKN2A/2B were measured in 322 ischemic stroke patients using peripheral blood leukocytes. Methylation levels of 36 CpG sites around promoter regions of CDKN2A/2B were examined with BiSulfite Amplicon Sequencing. CarAC was quantified with Agatston score based on results of computed tomography angiography. Generalized liner model was performed to explore the association between methylation levels and CarAC. Results Of the 322 analyzed patients, 187 (58.1%) were classified as with and 135 (41.9%) without evident CarAC. The average methylation levels of CDKN2B were higher in patents with CarAC than those without (5.7 vs 5.4, p = 0.001). After adjustment for potential confounders, methylation levels of CDKN2B were positively correlated with cube root transformed calcification scores (β = 0.591 ± 0.172, p = 0.001) in generalized liner model. A positive correlation was also detected between average methylation levels of CDKN2B and cube root transformed calcium volumes (β = 0.533 ± 0.160, p = 0.001). Conclusions DNA methylation of CDKN2B may play a potential role in artery calcification.