BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

Objective To investigate the clinical value of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in the diagnosis and prognosis evaluation of liver cancer patients.Methods From April 2020 to April 2022,a total of 105 liver cancer patients and 105 liver cirrhosis patients admitted in the hospital were selected as the liver cancer group and cirrhosis group,and another 105 healthy volunteers who underwent physical examinations in the hospital were selected as the control group.Real-time fluorescence quantitative PCR(qPCR)was applied to detect the expression of serum hsa_circRNA_0002980 and hsa_circRNA_104348.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value and prognostic val-ue of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in liver cancer.Multivariate COX re-gression was performed to analyze the influencing factors of prognosis in liver cancer.Results The expression levels of serum hsa_circRNA_0002980 in the liver cancer group,liver cirrhosis group,and control group in-creased sequentially(P＜0.05),while the expression levels of serum hsa_circRNA_104348 decreased sequen-tially(P＜0.05).The levels of alanine aminotransferase and aspartate aminotransferase in the liver cancer group and the liver cirrhosis group were higher than those in the control group(P＜0.05),and the level of al-bumin was lower than that in the control group(P＜0.05).The area under the curve(AUC)for the diagnosis of liver cancer by hsa_circRNA_0002980 combined with hsa_circRNA_104348 was 0.888(95％CI:0.838-0.928),which was obviously higher than those of hsa_circRNA_0002980(Z=3.526,P＜0.001)and hsa_cir-cRNA_104348 alone(Z=2.184,P=0.029).The expression level of serum hsa_circRNA_0002980 in the poor prognosis group was lower than that in the good prognosis group(P＜0.05),and the expression level of ser-um hsa_circRNA_104348 and the proportion of TNM stage Ⅲ+Ⅳ were higher than those in the good progno-sis group(P＜0.05).The AUC for predicting prognosis in liver cancer patients by the combination of hsa_cir-cRNA_0002980 and hsa_circRNA_104348 was 0.870(95％CI:0.790-0.928),and there was no statistically significant difference compared to the AUC predicted separately by hsa_circRNA_0002980 and hsa_circRNA_104348(P＞0.05).The expression of serum hsa_circRNA_0002980,hsa_circRNA_104348 and TNM stage were influencing factors for the prognosis of liver cancer patients(P＜0.05).Conclusion The expression lev-el of hsa_circRNA_0002980 in the serum of liver cancer patients is relatively low,while the expression level of hsa_circRNA_104348 is relatively high.Both have certain clinical significance in the diagnosis and prognosis e-valuation of liver cancer.

Objective: To construct a deep learning model based on convolutional neural network(CNN)-long short term memory network(LSTM)-Attention to explore the correlation between meteorological and clinical factors and the incidence of ischemic stroke. Methods: A fusion model CNN-LSTM-Attention based on CNN, LSTM, and Attention was constructed by incorporating clinical data and meteorological data of ischemic stroke inpatients. The predictive performance of the model was evaluated by maximum prediction error and root mean square error(RMSE). The impact of different lag days on prediction performance was investigated by selecting lag periods ranging from 1 to 7 days. Results: In both short-term and long-term predictions, the CNN-LSTM-Attention fusion model(short-term: 1.5 and 0.6; long-term: 8.3 and 2.5) showed superior maximum prediction bias and RMSE compared to the LSTM model(short-term: 2.8 and 1.2; long-term: 19.5 and 5.5) and the CNN-LSTM model(short-term: 2.0 and 0.8; long-term: 11.2 and 3.3). After incorporating lag days, the maximum prediction deviation and RMSE for lags of 3 days(short-term: 0.7 and 0.4; long-term: 5.5 and 1.9) and 5 days(short-term: 0.8 and 0.3; long-term: 6.5 and 2.0) in both short-term and long-term forecasts were smaller than lags of 0 days(short-term: 1.5 and 0.6; long-term: 8.3 and 2.5). The maximum prediction deviation and RMSE in the short-term forecast were greater than lag 0 days for both lag 1 days(1.5 and 0.8) and lag 7 days(1.9 and 0.9). In the long-term forecast, the two indicators for lag 1 days(6.8 and 2.4) were lower than those for lag 0 days but higher than those for lag 3 days and 5 days. The maximum prediction deviation for lag 7 days(7.5) was lower than that for lag 0 days, but the RMSE(2.7) is higher than that for lag 0 days. Conclusion The established CNN-LSTM-Attention model demonstrates significant predictive value for the onset of ischemic stroke and can provide reference for the rational allocation of medical resources.

Objective To compare the application value of different nutritional assessment tools for peritoneal dialysis patients.Methods A total of 147 patients who were hospitalized for peritoneal dialysis in The Second Affiliated Hospital of Naval Medical University between Oct.2022 and Oct.2023 were enrolled by convenience sampling method.The nutritional assessment was carried out by using 3 assessment tools,including 7-point subjective global assessment(7-SGA),malnutrition inflammation score(MIS)and controlling nutritional status(CONUT).Correlation analyses were conducted between the nutritional assessment results and anthropometric measurements and blood biochemical indexes.Results The incidence of malnutrition assessed by 7-SGA,MIS,and CONUT were 53.74%(79/147),48.30%(71/147),and 76.19%(112/147),respectively.Both 7-SGA and MIS assessment revealed that the incidence of malnutrition in peritoneal dialysis patients＞60 years old was significantly higher than that in patients≤60 years old(both P＜0.01).Grouped by 7-SGA results,the body mass index(BMI),skeletal muscle mass,skeletal muscle mass index,phase angle,grip strength,upper arm circumference,upper arm muscle circumference,skinfold thickness,albumin and prealbumin levels in malnourished peritoneal dialysis patients were significantly lower than those in well-nourished peritoneal dialysis patients(all P＜0.05).The 7-SGA score was negatively correlated with age(P＜0.05),and was positively correlated with BMI,skeletal muscle mass,skeletal muscle mass index,phase angle,grip strength,upper arm circumference,upper arm muscle circumference,skinfold thickness,albumin,prealbumin,total protein,creatinine,and hemoglobin(all P＜0.05).Conclusion The incidence of malnutrition in peritoneal dialysis patients varies with the assessment tools used.7-SGA score has high correlation with anthropometric and blood biochemical indexes,and is effective,reliable,and practical.It is a good tool for nutritional assessment in patients undergoing peritoneal dialysis.

Skin wound healing is a complex multi-stage biological process.Severe skin injury or poor overall health of patients can significantly reduce the healing ability of skin,and it is easy to form chronic wounds.Traditional wound dressings have a single function and cannot promote wound healing.In recent years,functional hydrogels have shown great potential in skin wound repairing due to their natural extracellular matrix structure,adjustable mechanical properties and easy delivery of biologically active substances.This paper introduces the research advances in functional hydrogel dressings for skin wound repair.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Objective To investigate the effects of Toxoplasma gondii type Iand IIrhoptry protein 16 (ROP16) on the polarization and inflammatory response of mouse alveolar macrophages, so as to provide the scientific evidence for unveiling the immunoregulatory mechanisms following T. gondii infection in host cells and the clinical diagnosis and treatment of pulmonary toxoplasmosis. MethodsMouse alveolar macrophages served as blank controls, and mouse alveolar macrophages transfected with the empty lentiviral expression vector served as negative controls, and mouse alveolar macrophages transfected with lentiviral vectors overexpressing T. gondii type I and II ROP16 served as the type I and II ROP16 overexpression groups. Following puromycin selection, stably transfected cells that overexpressed type Iand IIROP16 were generated, observed for green fluorescence expression under a fluorescence microscope and verified using PCR, Western blotting and real-time quantitative reverse transcription PCR (RT-qPCR) assays. The expression of ROP16, inducible nitric oxide synthase (iNOS), arginase (Arg)-1, mannose receptor (CD206), cluster of differentiation 86 (CD86), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β proteins was determined in mouse alveolar macrophages using Western blotting assay, and the mRNA levels of ROP16, iNOS, IL-1β, IL-4, IL-12, IL-18, Arg-1, IL-10, IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β were detected in mouse alveolar macrophages using RT-qPCR assay. Results Fluorescence microscopy showed 90% of mouse alveolar macrophages producing green fluorescent signals in the type Iand II ROP16 overexpression groups and the negative control group. The relative ROP16 protein expression was 1.000 ± 0.000, 1.003 ± 0.020, 1.349 ± 0.055, and 1.376 ± 0.080 in mouse alveolar macrophages in the blank control group, negative control group, and type Iand IIROP16 overexpression groups (F = 35.30, P < 0.01), and the relative ROP16 mRNA expression was 1.007 ± 0.172, 2.030 ± 0.356, 1 409.579 ± 75.960, and 1 413.581 ± 27.712 in the blank control group, negative control group, and type Iand II ROP16 overexpression groups (F = 811.00, P < 0.01). The ROP16 expression was significantly higher in the type Iand IIROP16 overexpression groups than in the blank control group at both protein and mRNA levels (all P value < 0.01). Western blotting assay detected significant differences among the four groups in terms of iNOS, Arg-1, CD86, CD206, NLRP3, caspase-1, ASC, and IL-1β protein expression (F = 124.70, 82.40, 79.82, 919.40, 84.74, 39.85, 2 354.00 and 65.96, all P values < 0.05), and the expression of Arg-1, CD206, NLRP3, caspase-1, ASC, and IL-1β proteins was significantly higher in the type I ROP16 overexpression group than in the blank control group (all P values < 0.001), while the expression of iNOS, CD86, NLRP3, caspase-1, ASC, and IL-1β proteins was significantly higher in the type II ROP16 overexpression group than in the blank control group (all P values < 0.01). RT-qPCR assay detected significant differences among the four groups in terms of iNOS, IL-1β, IL-4, IL-12, IL-18, Arg-1, IL-10, IL-6, TNF-α, and TGF-β mRNA expression (F = 407.00, 1 528.00, 833.10, 267.90, 989.80, 161.80, 461.10, 5 529.00, 849.60 and 8 836.00, all P values < 0.05), and the Arg-1, IL-4, IL-10, and TGF-β mRNA expression was significantly higher in the type I ROP16 overexpression group than in the blank control group (all P values < 0.001), while the iNOS, IL-1β, IL-12, IL-18, IL-6, and TNF-α mRNA expression was significantly higher in the type II ROP16 overexpression group than in the blank control group (all P values < 0.001). Conclusions T. gondii type IROP16 may induce M2-dominant phenotypes of mouse alveolar macrophages, and type II ROP16 may induce M1-dominant phenotypes of mouse alveolar macrophages. Both T. gondii type I and II ROP16 may activate NLRP3, and mediate the activation of ASC, caspase-1 and IL-1β to promote inflammatory responses.

Objective To investigate whether the PI3K/AKT/Cdkn1a/GPX4 signaling axis participates in the pathogenesis of radiation-induced heart disease (RIHD) through the ferroptosis pathway. Methods An RIHD mouse model was established by irradiating C57BL/6J mice with 20 Gy X-rays. Transcriptomic sequencing, the FerrDb ferroptosis-related gene set, and weighted gene co-expression network analysis were used to identify hub genes associated with ferroptosis in RIHD. KEGG enrichment analysis was employed to determine key signaling pathways. An AC16 cardiomyocyte model of RIHD was constructed, and the optimal modeling conditions were determined using CCK-8 assays and flow cytometry. Reverse transcription-quantitative PCR and Western blotting were applied to validate the expression changes of key genes and pathways in cardiomyocytes. Results Compared with the control group, myocardial tissues from irradiated mice exhibited typical RIHD pathological alterations, including structural disorganization and degeneration. Bioinformatics analysis identified Cdkn1a and Ddit4 as potential hub genes, with the PI3K/AKT pathway as the key signaling pathway. The optimal conditions for establishing the RIHD cell model were determined to be 10 Gy irradiation and 48 hours of incubation. Cellular experiments confirmed that, compared with the control group (0 Gy), irradiated cardiomyocytes (10 Gy) showed significantly elevated CDKN1A expression (P < 0.01), inhibited phosphorylation of the PI3K/AKT signaling pathway (P < 0.05), downregulated GPX4 expression (P < 0.05), and induction of ferroptosis. Conclusion This study preliminarily clarifies the potential role of the PI3K/AKT/Cdkn1a/GPX4 signaling axis in regulating ferroptosis in RIHD cardiomyocytes, providing new therapeutic targets and strategies for the prevention and treatment of RIHD.