Objective To explore the role of E1A binding protein p300 (EP300)-mediated crotonylation (Kcr) modification of malic enzyme 1 (ME1) in ferroptosis of renal tubular epithelial cells. Methods C57BL/6 mice were divided into Sham operation group (Sham group), DMSO vehicle control + ischemia-reperfusion (IR) injury group (Vehi + IR group), and EP300 inhibitor C646 + IR injury group (C646 + IR group), with 12 mice in each group. Pathological changes in renal tissues were evaluated in each group, and indicators of renal function, ferroptosis, and fibrosis were assessed. Another 24 mice were used to establish the IR injury model to analyze changes in Kcr modification levels and EP300 expression over the 14-day course of IR injury. The in vitro HK-2 cell experimental model was established and divided into control group, hypoxia/reoxygenation (H/R) group, and C646 + H/R group. Corresponding HK-2 cells were transfected with the ME1-K337R plasmid, in which lysine 337 (K) was mutated to arginine (R) to mimic the de-Kcr modification. Small interfering RNA was used to target EP300 and transfect the cells in order to obtain EP300 knockdown cells (siEP300). The expression of ferroptosis-related proteins and fibrosis phenotypes was detected. Results At 14 d after IR injury, the protein Kcr level and EP300 expression were increased in mice. Compared with the Sham group, the Vehi+IR group showed markedly disrupted renal tissue structure, extensive red collagen deposition in the renal interstitium, decreased expression levels of glutathione, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione peroxidase 4 (GPX4, P＜0.01), increased malondialdehyde and serum creatinine levels (P＜0.01), decreased ME1 enzymatic activity (P＜0.001), and increased expression of fibronectin 1 and smooth muscle actin-α (P＜0.001). Compared with the Vehi+IR group, the C646+IR group showed alleviated renal pathological injury, improved renal function, and reduced ferroptosis and fibrosis (P＜0.05). Compared with the control group, HK-2 cells subjected to H/R treatment exhibited aggravated ferroptosis and fibrosis (P＜0.05); compared with the H/R group, the C646+H/R group showed reduced ferroptosis and fibrosis (P＜0.05). Transfection with the ME1-K337R plasmid and siEP300 showed reduced ME1 Kcr, ferroptosis, and fibrosis. Conclusions EP300 contributes to ferroptosis in renal tubular epithelial cells by mediating ME1 crotonylation, and inhibition of EP300 may help alleviate the chronic progression following IR injury.

Objective To explore the diagnostic value of 68Ga-PSMA-11 PET/CT combined with abnormal prothrombin(PIVKA-Ⅱ)in the diagnosis of different tumors.Methods A total of 200 patients with suspected cancer who underwent examinations in the Affiliated Hospital of Southwest Medical University from September 2021 to December 2023 were retrospectively selected,including 51 suspected liver cancer,49 suspected pancreatic cancer,52 suspected rectal cancer and 48 suspected prostate cancer.All patients underwent both serum PIVKA-Ⅱ testing and 68Ga-PSMA-11 PET/CT imaging.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic performance of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ for liver cancer,pancreatic cancer,rectal cancer and prostate cancer.Results No significant differences were found in general data of 4 suspected tumor groups(P>0.05)except for age.Serum PIVKA-Ⅱ levels were significantly higher in patients with suspected liver cancer and rectal cancer compared with those with suspected pancreatic cancer and prostate cancer(P<0.05).No significant difference was observed in the serum PIVKA-Ⅱ levels between suspected pancreatic cancer group and suspected prostate cancer group(P>0.05).The positive rates of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ for diagnosing liver,pancreatic,rectal,and prostate cancers were significantly lower than those of pathological examination(49.0%vs.47.1%vs.92.2%,57.1%vs.55.1%vs.87.8%,48.1%vs.44.2%vs.92.3%,64.6%vs.62.5%vs.89.6%,respectively,P<0.05).ROC curve analysis showed that serum PIVKA-Ⅱ had a sensitivity of 79.06%,specificity of 72.02%,area under ROC curve(AUC)of 0.822,and Youden index of 0.512.For 68Ga-PSMA-11 PET/CT,the sensitivity was 79.11%,specificity 72.07%,AUC 0.829,and Youden index 0.510.The combined use of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ achieved higher diagnostic accuracy,with a sensitivity of 93.28%,specificity of 81.15%,AUC of 0.924 and Youden index of 0.744,all surpassing the single index.Conclusion Both 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ are effective diagnostic tools for liver,pancreatic,rectal,and prostate cancers,with the combined approach yielding superior diagnostic performance.

Hypereosinophilia is the term given to a group of highly heterogeneous diseases that are characterized by an increase in the absolute count of peripheral eosinophils,which can accumulate in one or more organs.Although parasitic infection is one of the common causes of eosinophilia,it is often ignored.So far,no clear diagnostic guideline for hepatic sparganosis exists worldwide,and only scattered cases have been reported.We reported a case of a patient with hypereosinophilia induced by hepatic sparganosis,with multiple organ involvement,and discussed the clinical characteristics and treatment plan.This report will help clinicians better understand the differential diagnosis of hepatic sparganosis and the diagnosis and treatment of hypereosinophilia.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Objective:To evaluate the impact of implementing a regional hierarchical medical management model based on the medical internet of things (medical IoT) on the frequency of emergency department visits and hospitalizations, as well as related medical expenses, in patients with chronic obstructive pulmonary disease (COPD).Methods:This retrospective study included COPD patients enrolled in the regional hierarchical medical management system based on Medical IoT across 21 community health service centers in Songjiang District, Shanghai, between July 2017 and May 2018. Utilizing patient data from the year prior to enrollment as the baseline, changes in the number of emergency visits, hospitalizations, and associated medical costs during the first and second years of management were compared. Changes for patients receiving drug treatment were also analyzed.Results:A total of 973 COPD patients were enrolled. The mean age was 75.2±17.0 years, and 64.34% (626/973) were male. Compared to baseline, all COPD patients in the first year of management showed significant reductions: emergency visits decreased by 33.67%, total emergency costs by 45.60%, hospitalizations by 27.15%, and total hospitalization costs by 25.42%. In the second year, reductions were: emergency visits by 28.08%, total emergency costs by 36.10%, hospitalizations by 35.26%, and total hospitalization costs by 18.13% (all P<0.05). Among patients receiving drug therapy, reductions in the first year were: emergency visits by 39.66%, total emergency costs by 47.54%, hospitalizations by 25.19%, and total hospitalization costs by 28.40%. In the second year, reductions were: emergency visits by 46.98%, total emergency costs by 45.99%, hospitalizations by 41.98%, and total hospitalization costs by 24.94% (all P<0.05). No significant differences were observed before and after management for patients without drug treatment. Conclusion:The implementation of the regional hierarchical medical management model based on Medical IoT significantly reduced the frequency of emergency visits and hospitalizations, as well as related costs, for COPD patients.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective To report a rare clinical case of Rickettsia sibirica infection complicated with left ventricular apical thrombus,and to explore its pathogenesis,diagnosis and treatment strategies,as well as the significance of anticoagulant intervention.Methods Clinical analysis was performed on a 71-year-old female patient.The patient presented with fever,coma,and multiple organ damage.Combined with the presence of eschar on the left ankle and a history of contact with pet dogs,the diagnosis of Rickettsia sibirica infection was confirmed by blood metagenomic next-generation sequencing(mNGS).The patient was treated with doxycycline combined with vancomycin for anti-infection,and rivaroxaban for anticoagulation.Inflammatory indicators,coagulation function,cardiac ultrasound,and organ function were dynamically monitored.Results Blood mNGS detected Rickettsia sibirica(11 sequences,relative abundance 29.73%).The diagnosis was confirmed in combination with eschar,skin rash,and shock manifestations.After 4 days of anti-rickettsial treatment,the patient regained consciousness,body temperature and blood pressure returned to normal,and inflammatory and coagulation indicators improved significantly.Cardiac ultrasound showed a left ventricular apical thrombus(3.8 cm×2.4 cm).The thrombus persisted but remained asymptomatic after anticoagulant treatment.Rickettsia-induced vascular endothelial damage,hypercoagulable state,and reduced left ventricular systolic function[ejection fraction(EF)was 0.40]collectively contributed to the formation of the apical thrombus.Conclusions Rickettsia sibirica infection can lead to intracardiac thrombus(the first reported case),with mechanisms related to endothelial damage,hypercoagulable state,and cardiac insufficiency.mNGS has key value in the rapid identification of pathogens in patients with fever of unknown origin accompanied by shock.Doxycycline is a core effective drug for rickettsial infections,and early anticoagulant intervention is required for patients with complicated thrombus.A history of pet contact and skin eschar are important epidemiological clues,which need to be strengthened in clinical identification.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Diabetic nephropathy(DN)is a significant causative factor of end-stage renal disease globally,and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways.Podocytes play crucial roles in the process of DN,with the extent of podocyte injury closely associated with key pathological manifestations of renal damage,such as proteinuria,glomerular filtration rate,and glomerulosclerosis.However,due to the complexity and interplay of mechanisms contributing to podocyte injury,such as oxidative stress,abnormal lipid metabolism,and mitochondrial damage,the precise mechanisms underlying podocyte injury remain incompletely understood.This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN.Furthermore,this article summarized the implications of these mechanisms for DN treatment,particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways,so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.