Mitochondrial dysfunction and disulfidptosis co-regulate neuronal cell in neuropathic pain based on bioinformatics analysis.

Neuropathic pain (NP) affects approximately 6.9-10% of the world's population and necessitates the development of novel treatments. Mitochondria are essential in the regulation of cell death. Neuroimmune mechanisms are implicated in various forms of cell death associated with NP. However, the specific involvement of mitochondrial dysfunction and disulfidptosis in NP remains uncertain. Further research is required to gain a better understanding of their combined contribution. Our comprehensive study employs a variety of bioinformatic analysis methods, including differential gene analysis, weighted gene co-expression network analysis, machine learning, functional enrichment analysis, immune infiltration, sub-cluster analysis, single-cell dimensionality reduction and cell-cell communication to gain insight into the molecular mechanisms behind these processes. Our study rationally defines a list of key gene sets for mitochondrial dysfunction and disulfidptosis. 6 hub mitochondrial genes and 3 disulfidptosis-related genes (DRGs) were found to be associated with NP. The key genes were predominantly expressed in neurons and were lowly expressed in the NP group compared to SHAM. In addition, our macrophages used the APP (Amyloid precursor protein)-CD74 (MHC class II invariant chain) pathway to interact with neurons. These results suggest that NP is interconnected with the mechanistic processes of mitochondrial dysfunction and disulfidptosis, which may contribute to clinically targeted therapies.

Grape seed-derived procyanidins decreases neuropathic pain and nerve regeneration by suppression of toll-like receptor 4-myeloid differentiation factor-88 signaling.

Background: Recent studies have shown that peripheral nerve regeneration process is closely related to neuropathic pain. Toll-like receptor 4 (TLR4) signaling was involved in different types of pain and nerve regeneration. TLR4 induced the recruitment of myeloid differentiation factor-88 adaptor protein (MyD88) and NF-κB-depended transcriptional process in sensory neurons and glial cells, which produced multiple cytokines and promoted the induction and persistence of pain. Our study aimed to investigate procyanidins's effect on pain and nerve regeneration via TLR4-Myd88 signaling. Methods: Spinal nerve ligation (SNL) model was established to measure the analgesic effect of procyanidins. Anatomical measurement of peripheral nerve regeneration was measured by microscopy and growth associated protein 43 (GAP43) staining. Western blotting and/or immunofluorescent staining were utilized to detect TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), ionized calcium-binding adapter molecule 1 (IBA1) and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on pain and nerve regeneration. Result: Procyanidins reduced mechanical allodynia, thermal hyperalgesia and significantly suppressed the number of nerve fibers regenerated and the degree of myelination in SNL model. Compared with sham group, TLR4, MyD88, IBA1 and phosphorylation of NF-κB-p65 were upregulated in SNL rats which were reversed by procyanidins administration. Additionally, procyanidins also suppressed activation of spinal astrocytes and glial cells. Conclusion: Suppression of TLR4-MyD88 signaling contributes to the alleviation of neuropathic pain and reduction of nerve regeneration by procyanidins.

Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study.

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.

Factors associated with afebrile presentation and delayed defervescence of bacterial meningitis in children under 3 years of age: a multi-centre retrospective analysis.

BACKGROUND: This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. METHODS: Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. RESULTS: A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P < 0.05). The patients with fever were assigned into early and delayed defervescence groups based on defervescence time (less than and more than or equal to one week). Furthermore, Streptococcus agalactiae meningitis (OR = 1.124), concomitant gastrointestinal infection (OR = 1.276), encephalomalacia (or = 1.339), and subdural effusion (OR = 1.454) were independently associated with delayed defervescence (all P < 0.05). CONCLUSIONS: The findings can aid in the efficient utilization of fever in auxiliary diagnosis and evaluating the condition of the disease.

Evaluation of the combined predictive value of multiple indicators based on diaphragmatic ultrasound using logistic regression and ROC curve in weaning from mechanical ventilation in pediatric patients.

Background: Conventional single indicators have low sensitivity and specificity for predicting weaning from mechanical ventilation in pediatric patients, necessitating the establishment of a combined prediction model for predicting weaning outcomes. Objectives: To explore the combined predictive value of PaO2/FiO2 Ratio (P/F ratio), diaphragm excursion-rapid shallow breathing index (DE-RSBI), diaphragm thickening fraction-rapid shallow breathing index (DTF-RSBI), and Pediatric Critical Illness Score (PCIS) in weaning from mechanical ventilation in pediatric patients. Methods: Sixty critically ill pneumonia pediatric patients requiring mechanical ventilation treatment from July 2022 to June 2023 at the Second Affiliated Hospital of Jiaxing University were selected. They all underwent a spontaneous breathing trial (SBT) and were divided into the weaning success group (42 cases) and weaning failure group (18 cases) based on the weaning outcome. Parameters including total duration of illness, mechanical ventilation duration, heart rate (HR), P/F ratio, diaphragm excursion (DE), DE-RSBI, diaphragm thickening fraction (DTF), DTF-RSBI, and PCIS were included in univariate and multivariate logistic regression analyses to determine independent factors affecting pediatric weaning success. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of P/F ratio, DE-RSBI, DTF-RSBI, PCIS alone or in combination for weaning success. Results: Comparing P/F ratio, DE, DE-RSBI, DTF, DTF-RSBI and PCIS, there were statistically significant differences (P < 0.05). Through collinearity analysis and binary logistic regression analysis,P/F ratio [OR = 0.777, 95% CI (0.641,0.941)], DE-RSBI [OR = 1.694, 95% CI (1.172, 2.447)], DTF-RSBI [OR = 1.057, 95% CI (1.002, 1.114)], and PCIS [OR = 0.661, 95% CI (0.445, 0.982)] were identified as independent factors affecting successful weaning(P < 0.05).The regression equation was: LogitP = 73.299-0.253 P/F ratio + 0.525DE-RSBI + 0.055DTF-RSBI-0.43PCIS.The sensitivity of the combined indicator Logit(P) in predicting successful weaning from mechanical ventilation in pediatric patients was 88.9%, with a specificity of 95.2% (optimal cutoff value of 0.511), and the area under the ROC curve (AUC) was 0.960 [95% CI (0.915, 1.000)]. The AUC of the combined prediction model for predicting pediatric weaning was greater than that of P/F ratio, DE-RSBI, DTF-RSBI and PCIS alone (Z values = 9.129, 2.061, 2.075, 8.326, P < 0.05). Conclusions: In mechanically ventilated pediatric patients, the combined prediction model has better predictive value for weaning success compared to using P/F ratio, DE-RSBI, DTF-RSBI, or PCIS alone.