This study aimed to investigate the effect of atractylenolide I (Atr-I) on myocardial mitochondrial function in mice with dilated cardiomyopathy (DCM) by regulating the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. Sixty SPF-grade male cTnT R141W transgenic DCM mice were randomly divided into the DCM group, Atr-I low-dose group (60 mg/kg), Atr-I high-dose group (240 mg/kg), captopril group (0.01 g/kg), and Atr-I high-dose+cGAS/STING pathway activator 5,6-dimethylxanthenone-4-acetic acid (DMXAA) group, with 12 mice in each group. Additionally, 12 male C57BL/6J mice were used as the control group. All mice were administered via oral gavage once daily for 8 weeks. Cardiac function was assessed using the Vevo 770 ultrasound system; myocardial pathology was examined via HE staining; mitochondrial ultrastructure in cardiomyocytes was observed using transmission electron microscopy; the proportion of cardiomyocytes without reduced mitochondrial membrane potential was detected using JC-1 staining; reactive oxygen species (ROS) content in myocardial tissue was measured using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining; adenosine triphosphate (ATP) content in myocardial tissue was determined using a commercial kit; and Western blot was performed to detect the protein expression levels of mitofusin-2 (MFN2), dynamin-related protein 1 (DRP1), cGAS, STING, interferon-β (IFN-β), CXC chemokine ligand 10 (CXCL10), and interleukin-6 (IL-6) in myocardial tissue. The aim was to observe the effect of Atr-I on myocardial mitochondrial function in DCM mice. The results showed that low- and high-dose Atr-I (60 mg/kg, 240 mg/kg) intervention improved cardiac function, alleviated cardiomyocyte hypertrophy and disordered muscle fiber arrangement, ameliorated mitochondrial ultrastructure in cardiomyocytes, reduced ROS content and the protein expression levels of DRP1, cGAS, STING, IFN-β, CXCL10, and IL-6 in myocardial tissue, and increased the proportion of cardiomyocytes without reduced mitochondrial membrane potential, as well as ATP content and MFN2 protein expression in myocardial tissue. However, DMXAA attenuated the beneficial effects of high-dose Atr-I on myocardial mitochondrial function in DCM mice. In conclusion, Atr-I may improve myocardial mitochondrial function in DCM mice by inhibiting the cGAS/STING pathway.

ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

ObjectiveTo address the challenges of unstructured classical Chinese expressions， nested entity relationships， and limited annotated data in famous traditional Chinese medicine（TCM） case records， this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping， aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction（CasRel） model for TCM semantics was designed， integrating a pre-trained bidirectional encoder representations from transformers（BERT） layer for classical TCM texts to enhance semantic representation， and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model， combining data augmentation and entity mapping， outperformed the pipeline-based Bert-Radical-Lexicon（BRL）-bidirectional long short-term memory（BiLSTM）-Attention model. The overall precision， recall， and F₁-score across 12 relation types reached 65.73%， 64.03%， and 64.87%， which represent improvements of 14.26%， 7.98%， and 11.21% compared to the BRL-BiLSTM-Attention model， respectively. Notably， the F₁-score for tongue syndrome relations increased by 22.68%（69.32%）， and the prescription-syndrome relations performed the best with the F₁-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts， offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation， prescription optimization， and drug compatibility， providing a methodological reference for TCM artificial intelligence research.

ObjectiveTo observe the effect of heat-sensitive moxibustion on quality of life and immune function in non-small cell lung cancer （NSCLC） patients undergoing chemotherapy. MethodsSeventy NSCLC patients with qi deficiency and phlegm stasis syndrome were randomly divided into an intervention group and a control group， with 35 cases in each group. The control group received chemotherapy combined with routine symptomatic treatment， while the intervention group additionally received heat-sensitive moxibustion since the first day of chemotherapy. Acupoints included Dazhui （GV14）， bilateral Feishu （BL13）， Zhongwan （CV12）， Qihai （CV6）， and Guanyuan （CV4）. The site exhibiting the strongest heat-sensitization response was selected for moxibustion. Treatment was administered for 45 minutes per session， three times weekly for three consecutive weeks， totaling nine sessions. Before and after treatment， quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire （EORTC QLQ-C30）， and traditional Chinese medicine （TCM） syndrome scores were evaluated. Peripheral blood levels of natural killer （NK） cells and T-lymphocyte subsets including CD3⁺， CD4⁺， and CD8⁺， and CD4⁺/CD8⁺ ratio were measured. Levels of programmed cell death protein-1 （PD-1）， including PD-1⁺CD4⁺ and PD-1⁺CD8⁺ cells， were also assessed. Liver and renal function were monitored before and after treatment， and adverse events were recorded. ResultsIn the intervention group， 1 participant withdrew and 1 was excluded， while in the control group， 2 participants withdrew. Ultimately， 33 participants in each group were included in the final analysis. The intervention group showed significant improvements in physical， role， emotional， cognitive， and social functioning， as well as global health status after treatment， while scores for fatigue， nausea and vomiting， dyspnea， appetite loss， diarrhea， and TCM syndrome scale were significantly decreased （P＜0.05）. Moreover， the intervention group demonstrated higher scores in physical functioning， role functioning， and global health status， as well as lower scores for fatigue， nausea and vomiting， dyspnea， appetite loss， diarrhea， and the TCM syndrome scale than the control group （P＜0.05）. After treatment， the levels of peripheral NK cells and PD-1⁺CD8⁺ T cells in the intervention group increased significantly； furthermore， the intervention group exhibited higher peripheral NK cell levels and lower PD-1⁺CD8⁺ T cell levels than the control group （P＜0.05）. No significant differences were found in liver or renal function between the two groups （P＞0.05）. In addition， no adverse events such as burns or moxibustion-induced syncope occurred during the study. ConclusionHeat-sensitive moxibustion as an adjunctive therapy may enhance immune function， alleviate clinical symptoms， and improve quality of life， while demonstrating a favorable safety profile in NSCLC patients with qi deficiency and phlegm stasis.

BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective:To investigate the effects of body habitus and gender on radiation dose assessment methodologies in low-dose chest CT, with particular emphasis on clarifying discrepancies among various dose quantification approaches and their associations with patient characteristics.Methods:Imaging data from 19 371 patients who underwent low-dose chest CT at the First Affiliated Hospital of Chongqing Medical University between January 2021 and January 2024 were retrospectively analyzed. Patients were categorized into eight groups based on water-equivalent diameter (WED) and gender: Group A (150 mm≤WED<210 mm; 71 males, 1 032 females), Group B (210 mm≤WED<260 mm; 4 525 males, 8 005 females), Group C (260 mm≤WED<300 mm; 4 234 males, 1 105 females), and Group D (WED≥300 mm; 357 males, 42 females). WED, size-specific dose estimate (SSDE), and organ dose-based effective dose(ED Radimetrics)were calculated using Radimetrics software. Scanner-reported dose metrics, including volume CT dose index (CTDIvol), dose-length product (DLP), and DLP-derived effective dose(ED DLP), were recorded. The ratios of SSDE/CTDIvol and ED Radimetrics/ED DLP were used to quantify discrepancies between dose evaluation methods. The Kruskal-Wallis test was employed to analyze dose metric differences across WED groups within the same gender, while the Wilcoxon rank-sum test compared gender-based differences within each WED group. Results:All dose metrics significantly increased with WED for both genders (all P<0.05). Within the same WED group, ED Radimetrics was significantly higher in females ( P<0.05), whereas ED DLP was higher in males ( P<0.05). The SSDE/CTDIvol ratio decreased with increasing WED, declining from 1.74 in Group A to 1.16 in Group D for females and from 1.68 to 1.12 for males. The ED Radimetrics/ED DLP ratio exhibited a decreasing trend with WED in females (1.82 to 1.30) but showed an initial increase in males (1.29 in Group A to 1.31 in Group B) before decreasing to 0.94 in Group D (all intergroup P<0.05). SSDE/CTDIvol and ED Radimetrics/ED DLP ratios of females were consistently higher than that of males within each WED group (all P<0.05). Conclusions:Patient body habitus and gender significantly influence radiation dose distribution in low-dose chest CT. Larger body habitus is associated with higher radiation doses, while females receive greater ED Radimetrics than males within comparable body habitus. Traditional dose metrics (CTDIvol and ED DLP) were underestimated for patients with small body sizes and female individuals.

Objective:To develop a deep learning model based on 3D super-resolution reconstruction technology and to analyze its feasibility and effectiveness in predicting paraglottic space invasion in hypopharyngeal cancer.Methods:A retrospective study was conducted involving 382 patients with hypopharyngeal squamous cell carcinoma treated at Qilu Hospital of Shandong University between January 2014 and December 2020. The cohort included 364 males and 18 females, with a mean age of 62±7 years. Patients were divided into a training set ( n=300) and a test set ( n=82) based on enrollment time. A generative adversarial network was used to perform 3D super-resolution reconstruction on contrast-enhanced CT images, improving spatial resolution by 16 times. A 2.5D deep learning strategy was employed to construct Resnet-NR and Resnet-SR models based on conventional and super-resolution images, respectively, to predict whether the paraglottic space was invaded. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). A multi-reader multi-case study was conducted to assess the impact of the artificial intelligence (AI) model on clinicians′ diagnostic capabilities. Results:The super-resolution model Resnet-SR achieved the highest accuracy in both the training set (AUC=0.87, 95% CI: 0.84-0.90) and the test set (AUC=0.88, 95% CI: 0.81-0.96), significantly outperforming traditional clinical indicators (T stage, N stage, tumor diameter, and pathological differentiation degree) (AUC range: 0.55-0.70, all P<0.05). In comparison, the conventional-resolution model Resnet-NR achieved AUCs of 0.81 (95% CI: 0.77-0.84, P=0.005) and 0.80 (95% CI: 0.71-0.89, P=0.184) in the training and test sets, respectively. Using Resnet-SR to assist clinical decision-making improved the diagnostic accuracy of junior physicians (AUC=0.793 without AI assistance vs. AUC=0.871 with AI assistance, P=0.012) and significantly reduced diagnosis time for clinicians of all experience levels (86.5 s without AI assistance vs. 82.5 s with AI assistance, t=2.01, P=0.032). Conclusion:This study successfully develops a deep learning model based on 3D super-resolution reconstruction technology, which can assist in preoperative prediction of paraglottic space invasion in hypopharyngeal cancer. The AI-assisted tool improves diagnostic accuracy for junior physicians and enhances diagnostic efficiency for clinicians across all experience levels.

Objective:To explore the survival and prognostic factors of a long-course venetoclax-based(VEN-based)regimen in patients with de novo acute myeloid leukemia(AML)and provide evidence for the maintenance treatment of AML.Methods:A retrospective study was conducted in patients who received a VEN-based regimen and completed at least four courses of efficacy evaluation at The First Affiliated Hospital of Nanchang University from May 2021 to January 2024.The composite complete response rate(cCR),minimal residual disease(MRD)-negative rate,overall survival(OS)time,relapse-free survival(RFS)time,and adverse events were analyzed.Results:Overall,30 newly diagnosed patients with AML were enrolled in this study.The median age was 65(range,53-78)years,and the median number of treat-ment cycles was 7(range,4-20)years.After one cycle,the CR-and MRD-negative rates were 80.0%and 63.3%,respectively.The cumulative cCR was 96.7%,and MRD negative rate was 80.0%,respectively.The median follow-up time was 21.3(95%confidence intervals 14.7-27.9)months.The median OS time was 32.3 months and RFS time was not reached.The 2-year OS and RFS rates were 70.6%and 54.8%,respect-ively.Univariate analysis suggested that ELN2017 risk stratification and relapse status affected RFS and OS(P<0.05).However,the multivari-ate analysis failed to reveal any relationship between these factors and survival(P>0.05).In terms of safety,hematological adverse events were the most common,followed by infections.Overall,the VEN-based regimen was tolerated for patients with AML.Conclusions:A long-course VEN-based regimen is effective and safe.More than half of patients survive for>2 years,and it can be used as an effective mainten-ance treatment option for patients with AML.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.