OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Objective To investigate the ameliorative effects of 4-hydroxybenzyl alcohol(4HBA)on energy metabolism in ischemic astrocytes(ASC).Methods Primary ASC were isolated from rat cortical tissue,and then randomly divided into control,oxygen-glucose deprivation/reoxygenation(OGD/R)group,low-,medium-and high-dose 4HBA groups(50,100 and 200 μmol/L),and edaravone group.Except for the control group,OGD/R injury models were established in a tri-gas incubator.The following parameters were measured:cell mortality,adenosine triphosphate(ATP)content,activities of mitochondrial ATP enzymes(Na+/K+-ATPase and Ca2+/Mg2+-ATPase),activities of mitochondrial complexes Ⅰ-Ⅴ,and expression of energy metabolism-related genes.Results Compared with the control group,the OGD/R group showed significantly higher cell mortality[(9.49±0.85)％vs(0.00±0.00)％,P＜0.01],along with obviously decreased ATP content,Na+/K+-ATPase activity,Ca2+/Mg2+-ATPase activity,and mitochondrial complex Ⅰ-V activities(P＜0.01).Compared with the OGD/R group,three 4HBA groups as well as the edaravone group exhibited significantly reduced cell mortality and elevated ATP content,Na+/K+-ATPase activity,and complex Ⅰ,Ⅲ,and V activities.The high-and medium-dose 4HBA groups and the edaravone group demonstrated increased Ca2+/Mg2+-ATPase activity,and the high-dose 4HBA group and edaravone group exhibited more enhanced complexⅡ activity,and the three 4HBA groups had elevated complex Ⅳ activity(P＜0.05,P＜0.01).Conclusion 4HBA exerts protective effect against ischemic injury in ASC by mitigating energy metabolism dysfunction and reducing cell death.

The probability of pulmonary infection in stroke patients with dysphagia will be multiplied,which may endanger the life of the patients,and is a major problem to be solved urgently in clinic.Stroke and dysphagia can both lead to intestinal flora disorders,destroy the intestinal barrier function and create the con-ditions for the migration of opportunistic pathogenic bacteria from the intestinal tract to the lungs,which may trigger or exacerbate the symptoms of pulmonary infections in the patients.Based on the theory of"microbe-gut-lung"axis,this article reviews the related studies on the disorder of intestinal flora caused by dietary chan-ges after stroke and dysphagia,and then leads to the migration of intestinal flora to the lungs,resulting in pul-monary infections,as well as the potential impact of aspiration on the pulmonary infections complicating dys-phagia after stroke.The potential impact of aspiration on post-stroke swallowing disorders and concomitant lung infections.In order to explore the potential mechanism of recurrent pulmonary infections in the patients with post-stroke dysphagia from the perspective of parenteral dissemination of intestinal flora,and to provide new ideas for subsequent clinical interventions.

Chikungunya fever is spreading continuously worldwide，posing a growing public health challenge alongside other arboviral diseases. This article systematically reviews the epidemiological characteristics of chikungunya fever，analyzes the pandemic potential of Aedes mosquito-borne diseases and discusses integrated prevention and control strategies for China in the context of increasing importation risk，drawing on containment practices from multiple countries and regions.

Chikungunya fever is spreading continuously worldwide，posing a growing public health challenge alongside other arboviral diseases. This article systematically reviews the epidemiological characteristics of chikungunya fever，analyzes the pandemic potential of Aedes mosquito-borne diseases and discusses integrated prevention and control strategies for China in the context of increasing importation risk，drawing on containment practices from multiple countries and regions.

Objective To investigate the ameliorative effects of 4-hydroxybenzyl alcohol(4HBA)on energy metabolism in ischemic astrocytes(ASC).Methods Primary ASC were isolated from rat cortical tissue,and then randomly divided into control,oxygen-glucose deprivation/reoxygenation(OGD/R)group,low-,medium-and high-dose 4HBA groups(50,100 and 200 μmol/L),and edaravone group.Except for the control group,OGD/R injury models were established in a tri-gas incubator.The following parameters were measured:cell mortality,adenosine triphosphate(ATP)content,activities of mitochondrial ATP enzymes(Na+/K+-ATPase and Ca2+/Mg2+-ATPase),activities of mitochondrial complexes Ⅰ-Ⅴ,and expression of energy metabolism-related genes.Results Compared with the control group,the OGD/R group showed significantly higher cell mortality[(9.49±0.85)％vs(0.00±0.00)％,P＜0.01],along with obviously decreased ATP content,Na+/K+-ATPase activity,Ca2+/Mg2+-ATPase activity,and mitochondrial complex Ⅰ-V activities(P＜0.01).Compared with the OGD/R group,three 4HBA groups as well as the edaravone group exhibited significantly reduced cell mortality and elevated ATP content,Na+/K+-ATPase activity,and complex Ⅰ,Ⅲ,and V activities.The high-and medium-dose 4HBA groups and the edaravone group demonstrated increased Ca2+/Mg2+-ATPase activity,and the high-dose 4HBA group and edaravone group exhibited more enhanced complexⅡ activity,and the three 4HBA groups had elevated complex Ⅳ activity(P＜0.05,P＜0.01).Conclusion 4HBA exerts protective effect against ischemic injury in ASC by mitigating energy metabolism dysfunction and reducing cell death.

Ferroptosis is a form of regulated cell death that depends on iron and reactive oxygen spe-cies.Different from apoptosis,necrosis,and autophagy,ferroptosis is characterized by the accumulation of lipid peroxides in cells.Studies have discovered that ferroptosis is closely associated with the occurrence and develop-ment of tumors and inducing ferroptosis in tumor cells can enhance the therapeutic effects of drugs on tumors.This article summarizes the latest research progress in ferroptosis regarding its mechanisms and associations with tumors,aiming to provide a reference for further understanding the interaction mechanisms between ferroptosis and tumors and offering new insights and targets for the treatment of tumors.

Age-related hearing loss(ARHL)is a common chronic disease that poses a serious threat to the physical and mental health of the elderly in an aging society.It is a sensorineural hearing loss characterized by the loss of auditory hair cells,stria vascularis lesions,apoptosis of spiral ganglia,and degeneration of the audi-tory central nervous system,reducing the quality of life of the patients.This article reviews the research progress in the relationship of ARHL with Alzheimer's disease,depression,and frailty,as well as the daily intervention in ARHL.This review aims to improve people's awareness and attention to the health hazards of ARHL and to delay the occurrence and development of ARHL by implementing daily intervention measures to form a healthy lifestyle.

Objective:To explore the application value and surgical experience of neuroendoscopic resection for pediatric patients with cerebellar tumors.Methods:This was a case series study.The clinical data and outcomes of 30 pediatric patients with cerebellar tumors treated through neuroendoscopic surgery in the Department of Neurosurgery, the Guizhou Hospital of Shanghai Children′s Medical Center and Guizhou Provincial People′s Hospital from January 2021 to January 2024 were retrospectively analyzed.Results:Twenty-six patients underwent total resection, 3 patients underwent subtotal resection, and 1 patient underwent biopsy.Postoperative pathological findings showed 9 cases of medulloblastoma, 3 cases of ependymoma, 17 cases of astrocytoma (5 cases of World Health Organization Grade Ⅰ, 3 cases of Grade Ⅱ, and 9 cases of Grade Ⅲ), and 1 case of cerebellar benign lesion.During the perioperative period, malignant arrhythmia occurred and induced death in 1 case, cerebellar mutism occurred in 12 cases, and ataxia occurred in 22 cases.During the 1-36 months of follow-up, 2 cases developed communicating hydrocephalus at the 2 nd and the 6 th month, respectively, and improved after ventriculoperitoneal shunt; cerebellar mutism was relieved to varying degrees after an average postoperative follow-up period of (115±23) days(46-194 days), and ataxia was alleviated after an average postoperative follow-up period of (127±42) days(27-173 days).Tumors relapsed in 5 cases during the last follow-up. Conclusions:Neuroendoscopy provides an alternative to the microscope for experienced operators to achieve the surgical exposure requirements during the resection of pediatric cerebellar vermis tumors.

Objective:To analyze the clinical characteristics of children with systemic lupus erythematosus (SLE) combined with thrombotic microangiopathy (TMA), and clarify the clinical outcomes and related risk factors of pediatric patients through their treatment and follow-up.Methods:This was a single-center retrospective case-control study. Children diagnosed with SLE combined with TMA between January 2017 and January 2023 at Beijing Children′s Hospital, Capital Medical University, were selected as the TMA group, and SLE children without TMA were selected as the control group.According to the prognosis, children in the TMA group were further divided into the good prognosis group and the poor prognosis group.The data of the children were collected, including age, gender, SLE disease activity, clinical presentations at the time of diagnosis and at the time of thrombosis, laboratory examinations, treatment strategies, prognosis, and follow-up results.The chi-square test and Z-test were used for comparison of count data.The t-test was used for comparison of metrological pairing data.The Fisher′s exact test was used to compare the differences between the 2 groups in categorical variables.The univariate Logistic regression was used to analyze the risk factors of poor prognosis. Results:There were 29 cases in the TMA group, and the incidence of TMA accounted for 2.53% of SLE patients; 33 cases were in the control group.The age at diagnosis of TMA was 13 years and 5 months (ranging from 9 years, 1 month and 5 days to 17 years and 4 months).The common clinical manifestations in order of prevalence were renal involvement (28 cases, 96.55%), hematologic involvement (26 cases, 89.66%), serous effusion (17 cases, 58.62%), rash (13 cases, 44.82%), and neurologic involvement (12 cases, 41.38%).Pleurisy or pericarditis, renal involvement and neurological involvement occurred more often in the TMA group than in the control group (17 cases vs.3 cases, 28 cases vs.10 cases, 12 cases vs.3 cases), and the TMA group showed less facial rash and arthritis than the control group (13 cases vs.25 cases, 4 cases vs.17 cases), and the differences were statistically significant (all P<0.05).The Systemic Lupus Erythematosus Disease Activity Index score in the TMA group [(24.14±9.42) scores] was significantly higher than that in the control group [(10.18±9.42) scores], and the difference was statistically significant ( t=3.233, P<0.05).The hemoglobin level, platelet count, and complement C3 level of the children in the TMA group were significantly lower than those in the control group, whereas the double stranded DNA antibody, lactate dehydrogenase, D-dimer, urea, creatinine, ferritin level, and urine protein quantitation were significantly higher than those in the control group, and the differences were statistically significant (all P<0.05).In the TMA group, 5 cases had decreased ADAMTS13 activity, and 5 cases had significantly increased complement C5b9.A total of 15 cases (51.72%) in the TMA group underwent renal biopsy, and 13 of them had combined renal TMA.In the TMA group, 28 patients (96.6%) received hormone therapy, 17 patients received plasma exchange, and 12 patients were treated with immunosuppressants and biologics; 19 patients (65.5%) improved, and 10 patients (34.5%) gave up the treatment due to deterioration of the disease.The urea level and peripheral blood fragmented erythrocyte rate in the good prognosis group were significantly lower than those in the poor prognosis group [(13.18±4.39) mmol/L vs.(21.16±10.14) mmol/L, t=2.975, P=0.006; 8/17 (47.06%) vs.7/7 (100%), χ2=5.929, P=0.015].The univariate Logistic regression analysis showed that the fragmented erythrocyte, ADAMTS13 activity and urea were the independent risk factors for poor prognosis (all P<0.05). Conclusions:SLE patients with moderate-to-severe disease activity, especially children with hemolytic anemia, thrombocytopenia, and renal dysfunction as prominent manifestations, should be alert to the risk of TMA.Early diagnosis and treatment are crucial.