Objective To explore the imaging findings of atypical teratoid/rhabdoid tumor(AT/RT)in the central nervous sys-tem of children and to improve the understanding of this disease.Methods A retrospective analysis was conducted on the imaging data of 55 children with AT/RT confirmed by pathology.Results Among the 55 AT/RT children,74.5％were under 3 years old,with a male-to-female ratio of 1.5∶1.Intracranial AT/RT appeared hyperdense or slightly hyperdense on CT scans and accompa-nied by calcification or hemorrhage occasionally.32 cases showed peripheral cystic changes in MRI images.38 cases showed heteroge-neous enhancement,9 cases showed ring-like or band-like enhancement.13 cases showed cerebrospinal fluid dissemination.The mean minimum apparent diffusion coefficient(ADC)value was(0.61±0.11)× 10-3mm2/s.Spinal AT/RT manifested as solitary or mul-tiple intramedullary and/or extradural lesions on MRI,which showed unclear boundary from the spinal cord.Hemorrhage within or at the edge of the lesion was seen in 2 cases,involvement of nerve roots and adjacent muscle tissues in 3 cases,and cerebrospinal fluid dissemination of the intracranial and spinal cord at varying degrees in 5 cases.Conclusion The imaging findings of pediatric AT/RT in the central nervous system are diverse,combining imaging characteristics with age of onset facilitates the accurate diagnosis.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Objective To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency,which was based on G protein-coupled receptor 41(GPR41)/GPR43-mediated mitogen-activated protein kinase(MAPK)signaling pathway.Methods The three-factor composite modeling method of eating disorder,diarrhea and fatigue was used to establish a model of spleen qi deficiency,and the rats were randomly divided into model,honey-processed Hedysari Radix,probiotics and blank groups with 15 rats per group.The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix.The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage.The blank and model groups were given the same dose of distilled water by gavage.Four groups were treated for 15 d with once a day.The expression levels of GPR41,GPR43,P38 MAPK,c-Jun N-terminal kinase(JNK)and extracellular regulatory protein kinase 1/2(ERK1/2)in colon tissues were detected by Western blotting.Results The relative expression levels of GPR41 in the blank,model,honey-processed Hedysari Radix and probiotics groups were 0.95±0.07,0.45±0.03,0.84±0.19 and 0.86±0.20;the relative expression levels of GPR43 were 1.17±0.11,0.41±0.06,0.66±0.03 and 0.57±0.01;the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01,0.43±0.01,0.39±0.01 and 0.36±0.02;the phosphorylated JNK/JNK ratios were 0.58±0.05,1.47±0.10,0.90±0.11 and 0.90±0.11;the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33,3.19±0.03,2.01±0.17 and 2.23±0.59,respectively.Compared with the model group,the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups(P＜0.05,P＜0.01).Conclusion The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.

The pregnant woman was 30 years old,G2P0.This singleton pregnancy at 22 weeks of gestation was screened for second-trimester ultrasound malformations,suggesting fetal aortic valve atresia,aortic stenosis with reverse blood flow,mitral valve atresia,and markedly enlarged left ventricle,which was considered for the diagnosis of hypoplastic left heart syndrome(HLHS).The pregnancy was terminated at our hospital and subsequently underwent genetic testing with results of heterozygous variants in the NOTCH1 gene,which can cause aortic valve disease type 1.The findings of the fetal autopsy were aortic valve atresia,mitral valve widening and thickening,and left ventricular enlargement with myocardial infarction.This report focuses on the ultrasound characteristics of HLHS with left ventricular enlargement and its hemodynamic changes in order to improve clinicians'understanding of the progressive changes in the disease phenotype of HLHS.

Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.

Aim To elucidate whether Astragaloside Ⅳcould ameliorate pathological myocardial hypertrophy and fibrosis via the EGR1-SIRT1-PPARα-SCAD signa-ling pathway in TAC mice.Methods After randomi-zing mice into groups,the Sham+AS-Ⅳ group and TAC+AS-Ⅳ group were intragastrically administered 20 mg·kg-1AS-Ⅳ once daily,whereas the Sham+NS group and TAC+NS group were given equivalent saline.Six weeks post-surgery,an evaluation of cardiac function was conducted,heart weight index was compu-ted,morphological alterations in heart were noted,vari-ations in collagen and myocardial hypertrophy indexes were analyzed,ATP content,free fatty acid content,hydroxyproline content,SCAD expression,and enzyme activity were measured,and an initial investigation into the protein expression of EGR1-SIRT1-PPARα-SCAD in myocardial tissues was undertaken.Results After AS-Ⅳ intervention,the heart weight index of TAC mice decreased(P＜0.01),LVAWd,LVAWs,LVPWd and LVPWs values decreased(P＜0.01,P＜0.05),EF％and FS％values increased(all P＜0.01),myocardial hypertrophy markers and collagen area decreased,FFA content,HYP content and collagen expression de-creased(all P＜0.01),SCAD enzyme activity and ex-pression increased(P＜0.01,P＜0.05),and ATP content increased(P＜0.01).The expression of EGR1 protein decreased,and the expression of SIRT1 and PPARα protein increased(all P＜0.01).Conclu-sions AS-Ⅳ may improve fatty acid oxidation via the EGR1-SIRT1-PPARα-SCAD signaling pathway,thereby ameliorating pathological myocardial hypertrophy and fibrosis in TAC model mice.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

BACKGROUND: There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA). METHODS: This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods. RESULTS: The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment. CONCLUSIONS A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.
Humans ; Tomography, X-Ray Computed/methods* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Artificial Intelligence ; Aged ; Pneumonia/diagnosis* ; Latent Class Analysis ; Adult