To summarize the clinical features and management of severe sinoatrial node dysfunction in anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, and to raise awareness of this rare but life-threatening complication. We retrospectively analyzed three patients with anti-NMDA receptor encephalitis who developed sinus arrest and reviewed similar published cases. PubMed, Web of Science Core Collection, and Google Scholar were searched for reports published between January 2005 and January 2025 using the terms “anti-N-methyl-D-aspartate receptor encephalitis,” “anti-NMDAR encephalitis,” “cardiac arrest,” “sinus node dysfunction,” “sinus arrest,” “sinus pause,” and “asystole.” Only cases with confirmed anti-NMDAR encephalitis, documented cardiac rhythm abnormalities, and sufficient clinical data were included. In our three patients, sinus arrest lasted 5.71, 9.23, and 6.20 s, occurring on hospital days 17, 6, and 15, respectively. One patient underwent teratoma resection and received a temporary pacemaker. All three patients regained normal sinus rhythm after immunotherapy and achieved favorable clinical outcomes. The literature review identified 25 additional cases. In a pooled cohort of 28 patients, most were young women; sinus arrest often coincided with seizures and generally manifested during the acute phase. Overall, 76.92

The integrity of hematopoietic stem cell (HSC) function is crucial for robust hematopoietic regeneration following stress. Inflammatory responses are pivotal drivers of HSC stress response, yet the precise modulation of inflammatory pathways remains incompletely defined. In this study, we identify the RNA helicase Mov10 as a negative regulator of stress-induced inflammatory pathways in HSC. Our study indicates that Mov10, which is critically required for HSC maintenance, is highly expressed in HSC, and its loss adversely affects HSC fitness and survival during hematopoietic stress induced by bone marrow transplantation and irradiation (IR). Mechanistically, Mov10 mitigates excessive inflammatory activation to sustain HSC functional integrity during hematopoietic stress, primarily by enhancing the translation of CAMP, which inhibits the interaction between TNF-α and its receptor TNFR1 and suppresses NF-κB activation. Overall, our results imply that Mov10 plays a critical role in averting functional failure of hematopoiesis under stress, presenting viable paths for the therapeutic intervention of relevant diseases.

Background:Ferroptosis is a novel form of regulated cell death driven by lipid peroxidation and oxidative stress, and has been implicated in the pathogenesis of periodontitis. The purpose of this study was to elucidate mechanisms by which NADPH oxidase 2 (NOX2) promotes ferroptosis in gingival epithelial cells and contributes to periodontitis in vivo. Methods:Periodontitis was induced in C57BL/6 mice by silk ligation and an in vitro model was established using lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) -stimulated CA9-22 gingival epithelial cells. Expression levels of NOX2, GPX4, SLC7A11 and NF-κB and JAK2-STAT3 pathway-related proteins were assessed by Western blotting. Lipid peroxidation was quantified by measuring malondialdehyde (MDA) levels and intracellular reactive oxygen species (ROS) were measured using the fluorescent probe DCFH-DA and detected via microscopy and spectrophotometry. The effects of NOX2 on alveolar bone loss were evaluated by micro-CT analysis and H&E and TRAP staining. Results:NOX2 expression was significantly elevated in the gingival tissues of periodontitis patients, the mouse model and Pg-LPS-stimulated CA9-22 cells. Mechanistically, we confirmed that Pg-LPS upregulated NOX2 by triggering the TLR4/NF-κB pathway. Gene silencing of NOX2 in vitro effectively suppressed ferroptosis as indicated by reduced ROS/MDA levels and restored expression of GPX4 and SLC7A11. Furthermore, H2O2 added to cell cultures to mimic ROS effects demonstrated that NOX2 mediated ferroptosis via ROS generation and JAK2-STAT3 activation. In vivo, pharmacological inhibition of NOX2 attenuated ferroptosis, mitigated alveolar bone loss, and ameliorated periodontal pathology in mice. Conclusions:NOX2 activation promoted periodontitis by driving ferroptosis via the ROS/JAK2-STAT3 pathway, highlighting its potential as a novel therapeutic target.

OBJECTIVE:This study aimed to develop and validate machine learning (ML) models for predicting the prognosis of status epilepticus (SE) patients with multisystem complications. METHODS:We developed predictive models using six ML algorithms: least absolute shrinkage and selection operator (LASSO) logistic regression, k-nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost). We systematically evaluated the prognostic performance of these models against established clinical scores. Specifically, we compared them with the Status Epilepticus Severity Score (STESS), the Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Imaging Abnormalities-Tracheal Intubation (ENDIT) score, and the Epidemiology-based Mortality Score in Status Epilepticus (EMSE). RESULTS:A total of 169 patients with SE were included in this study. In the test dataset, the areas under the curve (AUC) of the models were 0.660 for DT, 0.644 for RF, 0.663 for SVM, 0.689 for KNN, 0.825 for XGBoost, and 0.610 for LASSO logistic regression.The SHAP analysis revealed the top ten predictors contributing to the XGBoost model: hypoalbuminemia, nutritional risk score, age, ventilation duration, NCSE, GCS score, duration of impaired consciousness, creatinine level, APACHE II score, and CCI. CONCLUSION:Compared with the other models and scoring systems, XGBoost demonstrated superior predictive performance, suggesting its potential utility for the early identification of high-risk patients and timely clinical intervention. Hypoalbuminemia was identified as the most important prognostic factor, highlighting the critical role of systemic injury in determining adverse outcomes in SE patients treated within the neurocritical care setting.

Lysine is an essential amino acid for cellular functions, and its de novo biosynthesis pathway, conserved in fungi but absent in vertebrates, is a promising antifungal target. We systematically evaluated the essentiality of this pathway in Cryptococcus neoformans, a fatal fungal meningitis pathogen. We identified five key enzymes in the lysine synthesis pathway of C. neoformans. The resulting knockout strains failed to grow in lysine-deficient medium, and phenotypic defects were fully rescued by genetic complementation. Virulence factor assays showed impaired capsule and melanin production across all mutants. These strains also displayed increased susceptibility to temperature stress, oxidative stress, and antifungal drugs. In a murine systemic infection model, lung and brain fungal burdens were markedly reduced for lys1 Delta and lys9 Delta mutants, and survival times for all knockout-infected mice were significantly extended. Notably, mice infected with lys9 Delta remained asymptomatic for 60 days post-infection, with no detectable fungal cells in brain or lung tissues. These findings suggest that disrupting the lysine biosynthesis pathway represents a promising avenue for drug development against C. neoformans.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract characterized by a complex interplay of genetic, environmental, and immunological factors. Neutrophils, as a key component of the innate immune system, play a critical role in IBD pathogenesis due to their dysregulated infiltration, impaired apoptosis, and resultant epithelial damage during the disease process. Conventional approaches aimed at suppressing neutrophil activity have achieved only modest clinical efficacy and highlight the need for strategies that recalibrate neutrophil responses without compromising their essential antimicrobial functions. In this study, we employed high-throughput chemical screening using neutrophil-specific transgenic zebrafish larvae to identify compounds capable of modulating neutrophil homeostasis, and subsequently evaluating their efficacy in a dextran sodium sulfate (DSS)-induced IBD model. We identified epothilone B (Epo B), a traditional chemotherapeutic drug, as a potential therapeutic candidate for IBD. Our findings demonstrate that Epo B protects against IBD by promoting intestinal epithelial recovery, alleviating inflammatory responses, and rebalancing the gut microbiota. Mechanistically, Epo B selectively stimulates neutrophil apoptosis by targeting and enhancing Caspase-3 cleavage, thereby inhibiting neutrophilic inflammation. This study underscores the utility of in vivo high-throughput drug screening in IBD and highlights Epo B as a promising candidate for drug repurposing in IBD treatment, offering a novel therapeutic strategy by targeting neutrophil apoptosis.

Schaalia infections are uncommon, with Schaalia cardiffensis infections being exceptionally rare. A 66-year-old, penicillin-allergic female presented with fever, cough and purulent sputum. Chest computed tomography revealed bilateral pneumonia, right loculated empyema and right lower lobe atelectasis. Initial drainage cultures identified only Streptococcus oralis, but subsequent anaerobic enrichment and 16 S rRNA gene sequencing confirmed S. cardiffensis, an obligate anaerobe. Due to absent susceptibility data, we established initial antimicrobial susceptibility profile for S. cardiffensis. Successful management was achieved using alternative antibiotics combined with percutaneous drainagein. This first Chinese case of an empyema co-infected with S. cardiffensis and S. oralis highlights diagnostic challenges and provides crucial susceptibility guidance.

OBJECTIVE:We aimed to establish a quantitative electroencephalography-based prognostic prediction model specifically tailored for nontraumatic coma patients to guide clinical work. METHODS:This retrospective study included 126 patients with nontraumatic coma admitted to the First Affiliated Hospital of Chongqing Medical University from December 2020 to December 2022. Six in-hospital deaths were excluded. The Glasgow Outcome Scale assessed the prognosis at 3 months after discharge. The least absolute shrinkage and selection operator regression analysis and stepwise regression method were applied to select the most relevant predictors. We developed a predictive model using binary logistic regression and then presented it as a nomogram. We assessed the predictive effectiveness and clinical utility of the model. RESULTS:After excluding six deaths that occurred within the hospital, a total of 120 patients were included in this study. Three predictor variables were identified, including APACHE II score [39.129 (1.4244-1074.9000)], sleep cycle [OR: 0.006 (0.0002-0.1808)], and RAV [0.068 (0.0049-0.9500)]. The prognostic prediction model showed exceptional discriminative ability, with an AUC of 0.939 (95 % CI: 0.899-0.979). CONCLUSION:A lack of sleep cycles, smaller relative alpha variants, and higher APACHE II scores were associated with a poor prognosis of nontraumatic coma patients in the neurointensive care unit at 3 months after discharge. CLINICAL IMPLICATION:This study presents a novel methodology for the prognostic assessment of nontraumatic coma patients and is anticipated to play a significant role in clinical practice.

OBJECTIVE:Patients diagnosed with autoimmune encephalitis (AE) require admission to the neurological intensive care unit (ICU) when they exhibit clinical manifestations such as status epilepticus, central hypoventilation, and severe involuntary movements. In order to determine the predictors of ICU admission and prognosis for patients with AE admitted to the neurological ICU, we analyzed the clinical characteristics of this patient population.METHODS:This retrospective study analyzed 123 patients admitted to the First Affiliated Hospital of Chongqing Medical University between 2012 and 2021 who were diagnosed with AE based on serum and/or cerebrospinal fluid (CSF) AE-related antibody positivity. We divided these patients into two groups: those who received ICU treatment and those who did not. We evaluated patient's prognosis using the modified Rankin scales (mRS).RESULTS:Univariate analysis revealed that epileptic seizures, involuntary movements, central hypoventilation, symptoms of vegetative neurological disorders, increased neutrophil-to-lymphocyte ratio (NLR), abnormal electroencephalogram (EEG) findings, and different treatments were associated with ICU admission for patients with AE. Multivariate logistic regression analysis showed that hypoventilation and NLR were independent risk factors for ICU admission in AE patients. Univariate analysis showed that age and sex were related to prognosis in ICU-treated AE patients, and logistic regression analysis indicated that age was the only independent risk factor for prognosis in ICU-treated AE patients.CONCLUSION:Increased NLR, except for hypoventilation, is an indicator of ICU admission in AE patients. Although a large number of patients with AE require ICU admission, the overall prognosis is good, particularly in younger patients.

Introduction Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a new form of autoimmunity-mediated central nervous system disease. It is especially easy to misdiagnose when clinical symptoms and cerebrospinal fluid (CSF) indicators are similar to those observed in patients with tuberculous meningitis (TBM). Methods We retrospectively analyzed five cases of autoimmune GFAP astrocytopathy that were initially misdiagnosed as TBM. Results In the five reported cases, all but one patient had meningoencephalitis in the clinic, and all patients exhibited increased pressure, lymphocytosis, increased protein levels, and decreased glucose levels in their CSF results and did not have typical imaging findings of autoimmune GFAP astrocytopathy. TBM was the initial diagnosis in all five patients. However, we found no direct evidence of tuberculosis infection, and anti-tuberculosis treatment had inconclusive effects. Following a GFAP antibody test, the diagnosis of autoimmune GFAP astrocytopathy was made. Conclusion When there is a suspected diagnosis of TBM but TB-related tests are negative, the possibility of autoimmune GFAP astrocytopathy should be considered.

To study the role of neutrophil elastase (NE) in the sterilization process and tissue injury,we developed a mouse model of acute otitis media (AOM) by direct transtympanic inoculation with Streptococcus pneumoniae (S.pn) and intraperitoneal injection of NE specific inhibitors.We collected the middle ear tissues for histological examination and the middle ear lavage fluid (MELF) for NE enzyme activity detection,S.pn load determination,inflammatory cells quantification and cytokines measurement at day 1,3,5 after inoculation,respectively.Data showed that the activity of NE in MELF supernatant significantly increased and peaked at day 3 in S.pn infected mice,as compared with the PBS group.The levels of TP,LDH,TNF-α and IL-1β3 in MELF decreased after Sivelestat treatment,a NE specific inhibitor,while the S.pn load had no significant difference compared with control group.In summary,our study demonstrats that NE can enhance inflammatory response and aggravate tissue damage,but do not involve in bacterial clearance during S.pn AOM.

Objective To develop a model of secondary otitis media by Streptococcus pneumoniae (Spn) following influenza A virus (IAV) infection in C57BL/6 mice and explore its pathological mechanism.Methods C57BL/6 mice were infected intranasally with different doses of H1N1 (PR8).In 5 d later, the mice were inoculated with Spn via transbullar injection to induce secondary otitis media.Body weight and survival were observed daily in all the mice.Then the mice were killed in different time periods after Spn inoculation.The middle ear (ME) tissues were collected for histological examination by HE staining, and the middle ear lavage fluid (MELF) were harvested for cell counting and bacterial counting.ELISA was used to detect the contents of pro-inflammatory cytokines in the MELF.Results Antecedent PR8 infection led to death in the mice with Spn-induced otitis media, while simple Spn inoculation had no such effect.The changes of body weight and survival rate were in a dose-dependent manner of PR8 infection.There were more infiltrated inflammation cells and larger bacterial counts in the ME tissue of the model mice when compared with the mice after simple Spn inoculation.There were no significant differences in the production of proinflammatory cytokines IL-6 and IFN-γ among the model mice of secondary otitis media (P ＞ 0.05), whereas TNF-α showed a remarkable increase than the mice after simple Spn inoculation (P ＜ 0.05).Conclusion A model of secondary otitis media of Spn following influenza A virus infection mice is successfully established in C57BL/6 mice.

PURPOSE:Major depressive disorder (MDD) is a worldwide concern and devastating psychiatric disease. The World Health Organization claims that MDD leads to at least 11.9% of the global burden of disease. However, the underlying pathophysiology mechanisms of MDD remain largely unknown.EXPERIMENTAL DESIGN:Herein, we proteomic-based strategy is used to compare the prefrontal cortex (PFC) in chronic social defeat stress (CSDS) model mice with a control group. Based on pooled samples, differential proteins are identified in the PFC proteome using iTRAQ coupled with LC-MS/MS.RESULTS:Ingenuity Pathway Analysis (IPA) is then followed to predict relevant pathways, with the ephrin receptor signaling pathway selected for further research. Additionally, as the selected key proteins of the ephrin receptor signaling pathway, ephrin type-B receptor 6 (EphB6) and the ERK pathway are validated by Western blotting.CONCLUSION AND CLINICAL RELEVANT:Altogether, increased understanding of the ephrin receptor signaling pathway in MDD is provided, which implicates further investigation of PFC dysfunction induced by CSDS treatment.

Repulsive guidance molecule a (RGMa) is a membrane-bound protein that inhibits axon outgrowth in the central nervous system. Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent spontaneous seizures. To explore the role of RGMa in epilepsy, we investigated the expression of RGMa in patients with TLE, pilocarpine-induced rat model, and pentylenetetrazol kindling model of epilepsy, and then we performed behavioral, histological, and electrophysiological analysis by lentivirus-mediated overexpression of RGMa in the hippocampus of animal model. We found that RGMa was significantly decreased in TLE patients and in experimental rats from 6 h to 60 days after pilocarpine-induced seizures. In two types of epileptic animal models, pilocarpine-induced model and pentylenetetrazol kindling model, overexpression of RGMa in the hippocampus of rats exerted seizure-suppressant effects. The reduced spontaneous seizures were accompanied by attenuation of hippocampal mossy fiber sprouting. In addition, overexpression of RGMa inhibited hyperexcitability of hippocampal neurons via suppressing NMDAR-mediated currents in Mg2+-free-induced organotypic slice model. Collectively, these results demonstrate that overexpression of RGMa could be an alternative strategy for epilepsy therapy.

AIMS AND OBJECTIVESTo explore the characteristics of mortality among severe stroke patients, analyse their causes of death and provide evidence for improving the survival rate of stroke patients.BACKGROUNDStroke is an important fatal and disabling disease that poses a large burden on its patients, and its high death rates have caused substantial concern to the World Health Organization.DESIGNA retrospective case-control study.METHODSA total of 188 patients who died of stroke in the neurological intensive care unit of the First Affiliated Hospital of Chongqing Medical University from January 2012-December 2015 were selected as cases. Additionally, 188 stroke survivors from the same neurological intensive care unit were randomly selected as paired cases. The clinical characteristics of the severe stroke patient deaths were analysed, and a univariate analysis was conducted to determine potential mortality risk factors. A logistic regression analysis was then conducted to determine the independent risk factors of mortality.RESULTSWe investigated a total of 231 cases of death in neurological intensive care unit patients, 188 of whom died of stroke. Therefore, the death rate from stroke accounted for 81.3% of the total population, with ischaemic, haemorrhagic and mixed strokes accounting for 47.19%, 26.84% and 7.36% of the patients, respectively. The leading cause of death was central nervous system-related causes (central respiratory and circulatory failure, brain herniation), followed by multisystemic causes. The independent risk factors of death among the neurological intensive care unit patients were as follows: brain herniation (OR = 18.15), multiple organ failure (OR = 13.12), dyslipidemia (OR = 4.64), community-acquired lung infection (OR = 4.15), use of mechanical ventilation (OR = 3.37), hypoproteinemia (OR = 2.29), history of hypertension (OR = 2.03) and hospital-acquired pneumonia (OR = 1.75).CONCLUSIONSThe most common cause of death in stroke patients was damage to the central nervous system. Independent risk factors were brain herniation, multiple organ failure, dyslipidemia, community-acquired lung infection, the use of mechanical ventilation, hypoproteinemia, a history of hypertension and hospital-acquired pneumonia. Clinicians should be aware of the presence and possible effects of these conditions. Early prevention, monitoring and intervention to modify controllable risk factors will improve patient prognosis.RELEVANCE TO CLINICAL PRACTICEClinicians should be aware of the multiple independent risk factors of death and implement timely treatment measures to reduce the incidence of death in severe stroke patients.

Acute otitis media (AOM) is one of the most common bacterial infectious diseases in children aged 2 to 7 years worldwide. We previously demonstrated that interleukin-17A (IL-17A) promotes an acute inflammatory response characterized by the influx of neutrophils into the middle ear cavity during Streptococcus pneumoniae-induced AOM. In general, the inflammatory response is viewed as an effector that frequently causes local tissue damage. However, little is known about the pathogenic effects of IL-17A in AOM. Here, we investigated the pathogenic effects of IL-17A by using wild-type (WT) and IL-17A knockout (KO) mouse models. The results showed that the pathogenic effects of AOM, including weight loss, histopathological changes, and proinflammatory cytokine production, were more severe in WT mice than in IL-17A KO mice, suggesting that IL-17A aggravates tissue damage in AOM. Furthermore, these pathogenic effects were found to be dependent on p38 mitogen-activated protein kinase (MAPK) and could be reversed in the presence of a p38 MAPK-specific inhibitor. It was also demonstrated that IL-17A promoted the production of neutrophil myeloperoxidase (MPO) through the p38 MAPK signaling pathway, which was responsible for the middle ear tissue injury. These data support the conclusion that IL-17A contributes to middle ear injury through the p38 MAPK signaling pathway.

目的 建立肺炎链球菌性急性中耳炎小鼠模型,研究白细胞介素17A(interleukin 17A,IL-17A)促进中耳上皮细胞凋亡以及凋亡促进中耳组织损伤的作用.方法 鼓膜穿刺术建立C57BL/6小鼠和IL-17A缺陷鼠急性中耳炎模型.收集中耳灌洗液,ELISA检测灌洗液中炎症因子和损伤标志物的表达.中耳组织石蜡切片经TUNEL染色和HE染色,观察小鼠中耳上皮细胞的凋亡和中耳组织损伤程度.采用广谱的凋亡抑制剂Z-VAD-FNK抑制凋亡后,观察中耳组织损伤的变化.结果 IL-17A显著上调白细胞介素6(IL-6)、肿瘤坏死因子α(TNF—α)和髓过氧化物酶(MPO)表达,加重了中耳炎症.IL-17A还促进了上皮细胞的凋亡和黏膜损伤.抑制凋亡后,显著降低了IL-17A介导的炎症反应,减轻了中耳组织损伤.结论 IL-17A可促进上皮细胞凋亡,加重中耳组织损伤.

We have recently reported that neutrophils play a pivotal role in innate defense against Streptococcus pneumoniae (Spn) during mouse acute otitis media (AOM). However, the underlying mechanism remains unclear. By constructing models of pneumococcal AOM in C57BL/6 mice and using a specific inhibitor in vivo, we investigated the role of myeloperoxidase (MPO), one of the most important protein components of neutrophils. Experiment results showed a significant increase in MPO production of the recruited neutrophils in Spn-infected mice. Neutrophils killed Spn in a MPO-dependent manner. MPO facilitated the generation of reactive oxygen species (ROS), and consequently promoted Spn clearance at an early stage and exacerbated tissue damage. Moreover, MPO induced neutrophil apoptosis and necrosis, which, in turn, worsened tissue damage. In summary, our study demonstrates that neutrophil MPO plays a paradoxical role in bacterial clearance and tissue damage in pneumococcal AOM.