Jiao Liu’s research while affiliated with Chongqing Medical University and other places

Purpose To investigate the composition of respiratory viromes and their association with disease severity among hospitalized pediatric patients. Methods Clinical data and metagenomic next-generation sequencing (mNGS) results were collected from pediatric patients hospitalized at the Children’s Hospital of Chongqing Medical University between January 2022 and September 2023. The analyzed specimens included sputum and bronchoalveolar lavage fluid (BALF). Results The study included 229 patients (65.07% male, median age 3 years) with 25 sputum and 204 BALF samples, of whom 40.17% met the WHO criteria for severe acute respiratory infection (SARI). Herpesviruses were detected in 166 cases (72.49%), including 85 cases of cytomegalovirus (CMV), 64 cases of Epstein-Barr virus (EBV), 34 cases of human herpesvirus-7 (HHV-7), 12 cases of human herpesvirus-6 (HHV-6), and 6 cases of herpes simplex virus type 1 (HSV-1). Additionally, 53 cases of torque teno virus (TTV) and 7 cases of torque teno mini virus (TLMV) were detected. CMV prevalence was highest in neonates, while EBV peaked in the 3–6 year group (37.78%). HSV-1 and HHV-6 were predominantly identified in severe infections. Conclusion Herpesviruses, particularly CMV and EBV, were the most frequently detected viruses, followed by anelloviruses. The age-specific viral distribution patterns provide novel epidemiological perspectives for understanding pediatric respiratory pathogenesis, though their clinical significance requires validation through mechanistic studies. Clinical trial number Not applicable.

Background Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear. Methods We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis. Results We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6. Discussion We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.

Background Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation. Methods Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors (TLRs) 1–9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-β (TRIF) were detected via Western blot analysis. Results RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection. Conclusions Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.

Background This study provides the first systematic review and meta-analysis to identify the predictors of unfavorable prognosis of COVID-19 in children and adolescents. Methods We searched literature databases until July 2021 for studies that investigated risk factors for unfavorable prognosis of children and adolescents with COVID-19. We used random-effects models to estimate the effect size with 95% confidence interval (CI). Findings We identified 56 studies comprising 79,104 individuals. Mortality was higher in patients with multisystem inflammatory syndrome (MIS-C) (odds ratio [OR]=58.00, 95% CI 6.39–526.79) and who were admitted to intensive care (OR=12.64, 95% CI 3.42–46.68). Acute respiratry distress syndrme (ARDS) (OR=29.54, 95% CI 12.69–68.78) and acute kidney injury (AKI) (OR=55.02, 95% CI 6.26–483.35) increased the odds to be admitted to intensive care; shortness of breath (OR=16.96, 95% CI 7.66–37.51) increased the need of respiratory support; and neurological diseases (OR=5.16, 95% CI 2.30–11.60), C-reactive protein (CRP) level ≥80 mg/L (OR=11.70, 95% CI 4.37–31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76–236.44) increased the odds of progression to severe or critical disease. Interpretation Congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, MIS-C, shortness of breath, ARDS, AKI, gastrointestinal symptoms, elevated CRP and D-dimer are associated with unfavourable prognosis in children and adolescents with COVID-19.