Na Zang’s research while affiliated with Qingdao University and other places

Objectives This study aimed to examine the clinical characteristics and risk factors associated with the development of chronic critical illness (CCI) in children with sepsis. Methods A retrospective analysis was conducted on children diagnosed with sepsis and admitted to the Pediatric Intensive Care Unit (PICU) at Chongqing Medical University Affiliated Children's Hospital between January 2015 and December 2022. Patients were categorized into two groups based on clinical outcomes: CCI group, defined by an ICU stay ≥14 days with persistent organ dysfunction, and non-CCI group, including patients with rapid recovery or early death. Data on baseline demographics, clinical characteristics, and diagnostic and therapeutic differences were collected and analyzed. Results Among 1,326 children with sepsis, 244 were classified in the CCI group (135 males, 109 females) and 1,082 were classified in the non-CCI group (651 males, 431 females), including 163 cases in the early death group and 919 cases in the rapid recovery group. No significant differences were observed between the groups in terms of sex, age distribution, or prevalence of septic shock. Respiratory and gastrointestinal infections were the predominant sources of infection in both groups. Compared to the non-CCI group, the CCI group exhibited significantly higher weights, pediatric sequential organ failure assessment (pSOFA) scores, rates of underlying respiratory diseases, trauma, surgical interventions, mechanical ventilation duration, ICU stay, total hospital stay, and secondary infection rates. Multivariate logistic regression identified pSOFA score, underlying respiratory diseases, trauma, prolonged mechanical ventilation, surgical interventions, and secondary infections as independent risk factors for the development of CCI in children with sepsis. Based on ROC analysis, the AUC of the established CCI prediction model was 0.902 (95% CI: 0.873–0.928). Secondary infections were also a prominent clinical feature of CCI cases. Conclusions CCI in pediatric sepsis is associated with underlying respiratory diseases, trauma, elevated pSOFA scores, surgical procedures, prolonged mechanical ventilation and secondary infections. These factors contribute to extended hospital stays, elevated secondary infection rates, and poor clinical outcomes. The persistence of pro-inflammatory mediators and subsequent immunosuppression may underlie the development of CCI in this population.

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 Human adenovirus type 55 (HAdV-55) can lead to acute respiratory diseases, significant morbidity, and mortality in children. Methods Hospitalized children diagnosed with HAdV-55 between September 2016 and March 2024 at the Children’s Hospital of Chongqing Medical University were retrospectively analyzed. HAdV-55 was detected through polymerase chain reaction and sequencing. Clinical data were collected, including demographic characteristics, clinical manifestations, laboratory findings, imaging results, treatment history, and prognosis. A literature search was conducted using the PubMed database and China National Knowledge Infrastructure from their inception to June 2024. Search terms included “HAdV-55”, “HAdV-11a”, “adenovirus type 55” and their derivatives. Clinical features were evaluated in conjunction with literature on HAdV-55 infections in children. Results Five children with HAdV-55 infection were identified, including one mild, two severe, and two critical. The two critical patients exhibited progressive declines in total blood cell counts, hemoglobin levels and serum albumin levels within a short period. Adenoviral DNA was detected in pleural fluid or serum for them. They received mechanical ventilation, intravenous immunoglobulin, Methylprednisolone, blood transfusions, and antibiotics, while died for acute respiratory distress syndrome (ARDS). The remaining ones recovered and were discharged with good prognosis. A review of 56 cases, including those from this study, revealed that 61.9% (26/42) of infections were classified as severe or critical, with a mortality rate of 16.4% (9/55). Sequelae included bronchiolitis obliterans and bronchiectasis. Conclusions The genetic inheritance of HAdV-55 remained stable, with an upward trend of HAdV-55 severe infection among children from 2000 to 2019. Early clinical symptoms of HAdV-55 infection were overlapped with other respiratory viral infections. Rapid declines in blood cell counts, hemoglobin levels and serum albumin, along with dynamic monitoring of viral loads in sterile fluids, may serve as prognostic indicators.

Integrin alpha 2 (ITGA2) exhibits elevated expression in multiple cancer types. Nevertheless, its expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and its correlation with patient prognosis remains unclear. The aim of the present study was to examine the clinical relevance of ITGA2 expression in CESC. The expression of ITGA2 in CESC was investigated using The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis 2 databases. By comparing the ITGA2 median expression, all CESC samples were split into the two following groups: The ITGA2 high-expression and the ITGA2 low-expression groups. Subsequently, in order to determine the functional distinctions between the two groups, the following databases were used: Gene set enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology. The expression levels of ITGA2 were examined in cervical cancer cells using real-time reverse transcription-polymerase chain reaction and western blot analyses. Immunohistochemical staining was conducted to assess the expression levels of the ITGA2 protein in CESC and to examine the association of ITGA2 expression with the clinicopathological features and disease prognosis. According to the results obtained, patients with cervical cancer exhibited higher levels of ITGA2 expression. The overall survival and progression-free survival of patients with ITGA2-positive expression were considerably lower than those of patients with ITGA2-negative expression. The ITGA2 high-expression group demonstrated increased immune infiltration and elevated expression of immune checkpoint inhibitor targets. In conclusion, the data indicated that ITGA2 could be a novel tumor biomarker, which can be utilized for evaluating the prognosis and immunotherapy of patients with cervical cancer.

Increasing evidence suggests that human bocavirus (HBoV) is associated with respiratory symptoms in the absence of other identifiable pathogens and may even precipitate severe lower respiratory tract infections. However, only a few studies of severe human bocavirus infections in pediatric patients have been reported. The aim of the current study was to collect and analyze clinical data from children diagnosed with mild pneumonia and severe pneumonia, with an emphasis on those testing positive for HBoV from June 2009 to June 2019. Among the 799 HBoV‐positive children included in the study, approximately 5.88% experienced severe pneumonia. Results revealed no significant differences between co‐detection and single detection of HBoV‐positive pneumonia in the severe and mild groups, supporting the pathogenicity of HBoV. A higher incidence of severe cases was observed in children lacking Bacillus Calmette–Guérin (BCG) vaccination, or with congenital airway or bronchopulmonary dysplasia (P = 0.046, P = 0.017). Overall, these findings indicate that HBoV can be identified in respiratory samples from children with severe pneumonia, denoting its role as a viral pathogen in hospitalized children with this condition. Preterm birth, wheezing history of previous infection, pulmonary underlying diseases such as airway dysplasia or bronchopulmonary dysplasia, and viremia may be the risk factors for severe pneumonia with HBoV positive.

Background HAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown a significant increase in serum levels of vascular permeability factor (VPF/VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to the pulmonary vascular endothelium. Further research is necessary to elucidate the underlying mechanism. Methods The human lung microvascular endothelial cell line-5a and human CD46 mice were used for in vitro and in vivo experiments, respectively. RNA-seq was employed for correlative omics analysis. Viral infection and copy status were examined using transmission electron microscopy to observe virus particles, immunofluorescence to detect the viral protein Hexon, and qPCR to assess HAdV-7 fiber gene copies. Various methods, including ELISAs for VEGF and other injury markers, the CCK8 assay for cell viability, and flow cytometry for endothelium numbers, were employed to evaluate endothelial damage. Acute lung injury severity was evaluated by scoring pathological inflammation and measuring pulmonary vascular permeability. Autophagy activation was assessed by observing autophagosomes and validating marker proteins. Results GSEA analysis showed significant enrichment of gene sets related to endothelial functions (barrier, defense, and regeneration) and ALI in the HAdV-7-infected group. GO analysis indicated an enrichment of autophagy-related pathways linked to cell death. Subsequently, successful signs of HAdV-7 infection and replication were observed in the endothelium, including cytopathic effects, intracellular virions, and increased HAdV-7 fiber gene copies. Endothelial injury, including mitochondrial damage, decreased endothelium, and elevated levels of endothelial injury markers such as VEGF, sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, and IL1β were observed after HAdV-7 infection. Additionally, evidence of leaky lung blood vessels and ALI was observed, including progressive weight loss, elevated pulmonary vascular permeability, and severe lung consolidation. Furthermore, HAdV-7 infection induced autophagosome formation in the endothelium and triggered complete cell autophagy. Importantly, inhibiting autophagic flux reduced VEGF levels and other endothelial injury markers, decreased viral load, improved cell survival rate, alleviated pulmonary vessel leakage, and mitigated lung inflammation. Conclusions HAdV-7 successfully infects pulmonary vascular endothelium and replicates effectively, causing injury to the endothelium, high VEGF expression and viral load in the serum, as well as ALI/ARDS. Autophagy inhibitors can alleviate endothelial injury, inhibit viral replication, relieve leakage from the vasculature, and reduce lung inflammation.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales . RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV’s virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.