OBJECTIVE: To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis. METHODS: Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg^-1×d^-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting. RESULTS: On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05). CONCLUSION Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals ; Ferroptosis/drug effects* ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Sepsis/complications* ; Male ; Rats ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Neurons/drug effects* ; Signal Transduction ; Brain Injuries/metabolism* ; Flavonols ; Flavonoids/pharmacology* ; Heme Oxygenase-1/metabolism* ; Heme Oxygenase (Decyclizing)

Objective:To understand the current status, research hotspots, and future trends in the field of retinoblastoma (RB).Methods:Using the Web of Science Core Collection SSCI and SCI-Expanded as data sources, relevant RB literature from January 2015 to November 2024 was retrieved. The bibliometric analysis software CiteSpace 6.2.R6 was employed to perform visual analyses of countries/regions, institutions, journals, authors, co-cited references, and keywords.Results:A total of 5 042 relevant publications were identified. Annual publication numbers in this field consistently exceeded 400, peaking at 565 in 2021. The United States contributed the highest number of publications, with 1 600 articles (31.73%). Among institutions, Harvard University ranked first with 167 publications (3.31%). Abramson DH of Memorial Sloan Kettering Cancer Center published the most papers (75). Nature (United Kingdom) received the highest citation count (2 349). The highest betweenness centrality was observed for the United States (0.14) among countries/regions, Shanghai Jiao Tong University (0.21) among institutions, and Berry JL of Children’s Hospital Los Angeles (0.21) at the author level. Co-citation and keyword analyses revealed that RB research hotspots are shifting from a focus on basic molecular mechanisms, such as the cell cycle and RB protein, toward advanced therapeutic strategies, such as intra-arterial chemotherapy and nanoparticle-based drug delivery. Emerging keywords such as complexity, chemoresistance and carboplatin indicate that future studies will focus on optimising diagnosis and treatment. Conclusions:From 2015 to 2024, RB research displayed a sustained growth trend, with the United States and its institutions and scholars contributing the most publications. The research focus has shifted from the exploration of molecular mechanisms to the optimization of precise treatment strategies, among which the application of nanotechnology and the resolution of drug resistance mechanisms will become key breakthrough directions.

Aortic dissection(AD)is a life-threatening acute vascular disease with a complex and not yet fully un-derstood pathogenesis.In recent years,metabolic reprogramming has gradually emerged as a significant factor in the oc-currence and development of AD.This review summarizes the abnormal alterations in major metabolic pathways,including amino acid metabolism,glucose metabolism,and lipid metabolism,and their impact on vascular cell functions in AD.Metabolic reprogramming contributes to the progression of AD by regulating the functions of endothelial cells(EC)and vascular smooth muscle cells(VSMC),thereby promoting the destruction of the vascular wall structure and exacerba-ting inflammatory responses.Additionally,this paper summarizes the potential applications of metabolism-related mole-cules in the early diagnosis and treatment of AD,emphasizing the importance of metabolic regulation as a novel strategy for AD prevention and management.Finally,future research directions in the study of metabolic reprogramming in AD are proposed,including in-depth mechanistic studies,the development of novel biomarkers,and the optimization of clinical in-tervention strategies,aiming to provide new insights and methods for the prevention and treatment of AD.

Objective:To compare the accuracy of two-dimensional (2D) ultrasound with three-dimensional (3D) reconstruction and conventional 2D ultrasound in measuring bladder volume in pelvic tumor patients, using computed tomography (CT) as the reference.Methods:A set of bladder phantoms were constructed to compare CT and ultrasound measurements with actual injected volumes. Clinical data of 104 pelvic tumor patients who received radiotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences between August and December 2023 were retrospectively analyzed. Portable transabdominal ultrasound was used to obtain the largest bladder cross-section, and the maximum diameters in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions (D LR, D AP, D SI) were measured. The 2D ultrasound volume was calculated as V=0.523 × D LR × D AP × D SI. Full-bladder transverse videos were recorded and processed in Matlab R2016a through frame extraction(60 images), followed by contrast enhancement, edge detection segmentation, cubic spline interpolation, and image smoothing to achieve 3D reconstruction. Paired t-tests, intraclass correlation coefficients (ICC), and Bland-Altman analyses were performed to assess systematic bias and consistency between ultrasound methods and CT. Multivariate linear regression was applied to evaluate the effects of slice thickness, posture, age, and other factors on CT measurements. Results:In the phantom study, deviations of 2D ultrasound and CT from actual injected volumes were (0.73±3.05) ml ( t=-0.48, P=0.667) and (1.52±11.27) ml ( t=0.17, P=0.875), with ICC values>0.999. In the clinical study, mean bladder volumes measured by 3D-reconstructed ultrasound, conventional 2D ultrasound, and CT were (373.5±153.31), (314.89±135.28), (382.82±157.57) ml, respectively. The 3D-reconstructed method showed excellent agreement with CT (ICC=0.98; Bland-Altman mean bias=-9.32 ml, P=0.096), while 2D ultrasound also showed good consistency (ICC=0.91), but significantly underestimated bladder volume (mean bias=-67.93 ml, P<0.001). Subgroup analysis revealed that 2D ultrasound had the best agreement with CT in the medium-volume group (200-500 ml, ICC=0.902), whereas agreement decreased in the small-volume (<200 ml, ICC=0.884) and large-volume (>500 ml, ICC=0.840) groups (all P<0.001). The 3D-reconstructed ultrasound maintained excellent consistency with CT across all subgroups (all ICC>0.95), and the measured bladder volume was not statistically significant. Multivariate regression showed that slice thickness, posture, age, sex, and surgical status had no significant effects on CT measurements. Conclusions:Ultrasound with 3D reconstruction enables accurate bladder volume monitoring through true 3D contour reconstruction, while conventional 2D ultrasound systematically underestimates bladder volume and requires correction.

Objective To investigate the application of flipped classroom combined with teaching film-reading model in the teaching of filamentous fungal morphology for refresher doctors and evaluate its effect.Methods Fifteen refresher doctors taking microbiology from the 2022 batch of Guangdong Provincial People's Hospital were selected as the control group,and fifteen from the 2023 batch were se-lected as the experimental group.The"Morphological identification of Aspergillus and Mucor" was selected as the teaching content.The experimental group adopted flipped classroom combined with teaching film-reading model for teaching and the control group adopted tra-ditional teaching mode.The theoretical scores,operational scores,film-reading scores,and total scores of the two groups before and af-ter the implementation of teaching were compared and the teaching effect of the experimental group was evaluated using the Question-naire Star.Results The median scores of operational,film-reading,and total scores in the experimental group and control group were 40,30,and 95.5 and 36,27,and 85.5,respectively,and all the three scores in the experimental group were significantly higher than those in the control group(P＜0.05).Conclusion The flipped classroom combined with teaching film-reading model helps to improve the teaching effect of filamentous fungal morphology for refresher doctors,with high satisfaction,and can provide reference for subse-quent filamentous fungal morphology teaching.

This paper reports a pediatric patient with acute myeloid leukemia(AML)who developed bloodstream infection(BSI)caused by Trichosporon dohaense(T.dohaense).The pathogen in the blood culture of this case could not be identified by VITEK MS mass spectrometer;it was mistakenly identified as T.asahii by the VITEK ⅡYST system,and was ultimately accurately identified as T.dohaense through molecular sequencing.The(1-3)-β-D-glucan test(G test)result for this pediatric patient was within the normal range.The patient recovered and was discharged after active clinical antifungal treatment.Therefore,for T.dohaense BSI patients with granulocytope-nia,it is necessary to actively administer antifungal treatment in clinical practice,carefully interpret G test results,and further strengthen the understanding of this rare fungus.

This paper reports a case of fungal keratitis(FK)in a 62-year-old male patient who was infected with Colletotrichum fructicola(C.fructicola)after plant-related trauma.Pathogen from patient was not clearly identi-fied by two examination during hospitalization in other hospitals two months ago.Patient was confirmed with C.fructicola keratitis through confocal microscopy,corneal scraping,culture,and gene sequencing.The treatment of voriconazole combined with amphotericin B was adopted to enhance antifungal therapy,and anterior chamber irri-gation,drug(voriconazole)injection in anterior chamber and corneal stromal as well as corneal lesion removal were performed.The patient's symptoms were then improved.For patients with plant-related trauma keratitis,it is im-portant to be alert to the possibility of rare fungal infection.

Aortic dissection(AD)is a life-threatening acute vascular disease with a complex and not yet fully un-derstood pathogenesis.In recent years,metabolic reprogramming has gradually emerged as a significant factor in the oc-currence and development of AD.This review summarizes the abnormal alterations in major metabolic pathways,including amino acid metabolism,glucose metabolism,and lipid metabolism,and their impact on vascular cell functions in AD.Metabolic reprogramming contributes to the progression of AD by regulating the functions of endothelial cells(EC)and vascular smooth muscle cells(VSMC),thereby promoting the destruction of the vascular wall structure and exacerba-ting inflammatory responses.Additionally,this paper summarizes the potential applications of metabolism-related mole-cules in the early diagnosis and treatment of AD,emphasizing the importance of metabolic regulation as a novel strategy for AD prevention and management.Finally,future research directions in the study of metabolic reprogramming in AD are proposed,including in-depth mechanistic studies,the development of novel biomarkers,and the optimization of clinical in-tervention strategies,aiming to provide new insights and methods for the prevention and treatment of AD.

This paper reports a case of fungal keratitis(FK)in a 62-year-old male patient who was infected with Colletotrichum fructicola(C.fructicola)after plant-related trauma.Pathogen from patient was not clearly identi-fied by two examination during hospitalization in other hospitals two months ago.Patient was confirmed with C.fructicola keratitis through confocal microscopy,corneal scraping,culture,and gene sequencing.The treatment of voriconazole combined with amphotericin B was adopted to enhance antifungal therapy,and anterior chamber irri-gation,drug(voriconazole)injection in anterior chamber and corneal stromal as well as corneal lesion removal were performed.The patient's symptoms were then improved.For patients with plant-related trauma keratitis,it is im-portant to be alert to the possibility of rare fungal infection.

Objective To investigate the application of flipped classroom combined with teaching film-reading model in the teaching of filamentous fungal morphology for refresher doctors and evaluate its effect.Methods Fifteen refresher doctors taking microbiology from the 2022 batch of Guangdong Provincial People's Hospital were selected as the control group,and fifteen from the 2023 batch were se-lected as the experimental group.The"Morphological identification of Aspergillus and Mucor" was selected as the teaching content.The experimental group adopted flipped classroom combined with teaching film-reading model for teaching and the control group adopted tra-ditional teaching mode.The theoretical scores,operational scores,film-reading scores,and total scores of the two groups before and af-ter the implementation of teaching were compared and the teaching effect of the experimental group was evaluated using the Question-naire Star.Results The median scores of operational,film-reading,and total scores in the experimental group and control group were 40,30,and 95.5 and 36,27,and 85.5,respectively,and all the three scores in the experimental group were significantly higher than those in the control group(P＜0.05).Conclusion The flipped classroom combined with teaching film-reading model helps to improve the teaching effect of filamentous fungal morphology for refresher doctors,with high satisfaction,and can provide reference for subse-quent filamentous fungal morphology teaching.