Neutrophil extracellular trap-associated protein in cerebrospinal fluid for prognosis evaluation of adult bacterial meningitis: a retrospective case-control study.

BACKGROUND AND OBJECTIVES: Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. METHODS: This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. RESULTS: We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1ß, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1ß, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. CONCLUSION: The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.

Case Report: Encephalitis with Initial Manifestation of Orientia Tsutsugamushi Infection Detected by Metagenomic Next-Generation Sequencing.

Purpose: Scrub typhus, caused by Orientia tsutsugamushi, is characterized by fever, eschars, lymphadenopathy, and rash. The absence of eschars in some cases makes it difficult to distinguish it from other diseases, complicating the diagnosis process. Atypical Scrub typhus is difficult to diagnose and often leads to delayed treatment. Therefore, early diagnosis and treatment through effective detection methods have high clinical value. Here, a case of scrub typhus with encephalitis symptoms is reported. Patients and Methods: A 64-year-old man and mNGS testing. Results: A 64-year-old man developed cough, headache, and fever, dismissing it as a respiratory tract infection. Initial treatment with cephalosporin antibiotics had minimal effect. Admission to the respiratory department showed inflammation in blood tests. Subsequent CT and further treatment provided no improvement. Multidisciplinary discussions and neurology department guidance were conducted to consider the suspected diagnosis of encephalitis in the patient. After improving the mNGS detection, the patient was diagnosed with "Orientia tsutsugamushi encephalitis". After treatment with doxycycline, the patient's symptoms were alleviated. He remained afebrile in follow-up and adhered well to medical advice. Conclusion: Our case demonstrates that it is difficult to distinguish Orientia tsutsugamushi encephalitis from central nervous system infectious diseases such as meningitis and encephalitis using conventional diagnostic methods, which may affect the treatment plan for the disease. mNGS is a useful and valuable method for early diagnosis of scrub typhus.

Differential methylation of circRNA m6A in an APP/PS1 Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a chronic neurological disease characterized by memory loss and progressive cognitive impairment. The characteristic AD pathologies include extracellular senile plaques formed by ß­amyloid protein deposition, neurofibrillary tangles formed by hyper­phosphorylation of τ protein and neuronal loss caused by glial cell proliferation. However, the pathogenesis of AD is still unclear. Dysregulation of RNA methylation is associated with biological processes, including neurodevelopment and neurodegenerative disease. N6­methyladenosine (m6A) is the main modification in eukaryotic RNA and may be associated with the pathophysiology of AD. Circular RNA (circRNA) is a new type of evolutionarily conserved non­coding RNA without 5'­cap and 3'­polyadenylic acid tail. circRNA undergoes m6A RNA methylation and may be involved in the pathogenesis of AD. In the present study, high­throughput sequencing was performed to assess the degree of circRNA m6A methylation in APP/PS1 AD and C57BL/6 mice. These results suggested that circRNA m6A methylation in AD mice was markedly altered compared to the control group. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to predict associated pathways; genes with different circRNA m6A methylation in AD mice were associated with 'axon guidance', 'long­term potentiation', 'glutamatergic synapse', 'cholinergic synapse', 'GABAergic synapse' and 'long­term depression'. Methylated RNA immunoprecipitation reverse transcription­quantitative PCR demonstrated that among the eight selected circRNA m6A genes, there were five genes that demonstrated significantly increased methylation and three demonstrated significantly decreased methylation. In summary, the present study indicated that circRNA m6A methylation may be associated with pathogenesis of AD.