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.

This study aims to innovate a homogeneous outpatient service management system across multiple hospital campuses to enhance service quality.Based on the practical experience of a tertiary general hospital in Guangdong Province and in accordance with the"Interim Regulations on Outpatient Quality Management in Healthcare Institutions,"we constructed a"6+1"homogeneous outpatient service management system.This system includes:① a multi-stakeholder co-governance outpa-tient management system,②a vertical and cross-hierarchical management network,③ a democratic-centralized clinical coordina-tion strategy,④ a guidance-encouragement performance evaluation standard,⑤a collaborative dynamic supervision mechanism,⑥a spiral retrospective evaluation and improvement method,and ⑦ an integrated outpatient diagnosis and treatment system.Af-ter over two years of implementation,the hospital's outpatient volume has grown by an average of over 15％annually,patient waiting time after appointment has been reduced to 20 minutes,and patient satisfaction in the tertiary public hospital performance evaluation achieved full marks.The electronic medical record system functionality reached Level 6,significantly improving healthcare service efficiency and quality while enhancing homogeneous management across campuses.

Objective To compare the clinical efficacy of high-dose tigecycline(TGC)and polymyxin B(PMB)in the treatment of pulmonary infection due to carbapenem-resistant organism(CRO).Methods Clinical data of pa-tients with CRO pulmonary infection and received PMB or high-dose TGC combined with other antimicrobial treat-ment regimens in Department of Critical Care Medicine of Xiangya Hospital,Central South University from January 2019 to March 2022 were analyzed retrospectively,including basic information,pathogen detection results,antimi-crobial use regimen,clinical efficacy,30-day mortality,bacterial clearance rate,etc.Results A total of 173 pa-tients were included in analysis,with 103 in the TGC group and 70 in the PMB group.Compared with TGC group,PMB group had a higher score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)(25.0 vs 20.0,P＜0.001),but clinical efficacy rates were not statistically different(67.1％vs 52.4％,P=0.054).Stratified analysis revealed that when the APACHE Ⅱ score was ≥15 points,compared with TGC group(n=78),PMB group(n=66)had a higher APACHE Ⅱ score(27.0 vs 22.0,P=0.005)and a higher clinical efficacy rate(66.7％vs 47.4％,P=0.020).After adjusting confounding factors through logistic regression analysis,it was found that PMB treatment was a protective factor for clinical efficacy rate compared with TGC treatment.Conclusion For treating pulmonary infection caused by CRO in patients,PMB-based treatment regimen has a significant protec-tive effect on the clinical efficacy rate compared with the high-dose TGC-based treatment regimen.

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.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

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.