ObjectiveThis study aims to develop and validate a novel multimodal predictive model， termed criss-cross network（CCNet）-directed graph neural network（DGNN）（CGN）， for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer， by integrating longitudinal chest computed tomography（CT） imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron， and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently， a DGNN was constructed to integrate heterogeneous features， where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally， model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss， facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set， achieving an area under the receiver operating characteristic curve（AUC） of 0.830， accuracy of 0.843， sensitivity of 0.657， specificity of 0.712， Cohen's Kappa of 0.417， and F₁ score of 0.544. Compared with unimodal baselines， the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components， substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine （TCM）-specific symptomatology led to an additional 5% improvement in AUC， underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis， it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model， by synergistically combining cross-attention encoding with directed graph-based feature integration， enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment， thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.

OBJECTIVE: To investigate the metabolic characteristics of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in myeloid leukemia by in vitro culture of myeloid leukemia cells and construction of tumor-bearing nude mouse model. METHODS: U937, THP-1, HL60 and K562 cells were cultured in vitro. The cells in logarithmic growth phase (l×10 ⁵ cells/well) were added with ¹⁸F-FDG, and the uptake rate of ¹⁸F-FDG was measured at 15, 30, 60 and 120 min after addation, respectively. The four kinds of cells were inoculated subcutaneously into the hind limbs of nude mice to establish a tumor-bearing nude mouse model. When the tumor size was about 500 mm³, ¹⁸F-FDG was injected through the tail vein of the mice, and positron emission tomography/computed tomography was performed at 60 min after injection. The morphology of tumor-bearing cells was observed by hematoxylin-eosin (HE) staining in serial pathological sections. RESULTS: After co-incubation with ¹⁸F-FDG, the ¹⁸F-FDG uptake rates of U937 cells were significantly higher than THP-1, HL60 and K562 cells at 4 time points (all P <0.05), and THP-1 cells were higher than K562 cells (all P <0.05). The uptake rate of ¹⁸F-FDG by leukemia cells was rapid in the first 60 min, then tended to be stable. Pathological analysis showed that subcutaneous inoculation of U937, THP-1, HL60 and K562 cells could successfully establish tumor-bearing nude mouse models of myeloid leukemia. The ¹⁸F-FDG uptake value in U937 tumor-bearing nude mice was significantly higher than THP-1, HL60 and K562 tumor-bearing nude mice (all P <0.01). The ¹⁸F-FDG uptake values in THP-1 and HL60 tumor-bearing nude mice were significantly higher than that in K562 tumor-bearing nude mice (both P <0.01). CONCLUSION The tumor-bearing nude mouse model of myeloid leukemia can be successfully constructed by subcutaneous inoculation. The ¹⁸F-FDG uptake rate of acute myeloid leukemia (AML) cells is higher in cells cultured in vitro and tumor-bearing nude mouse model. ¹⁸F-FDG may have better clinical application value for AML.
Animals ; Fluorodeoxyglucose F18/metabolism* ; Mice, Nude ; Mice ; Humans ; Leukemia, Myeloid/diagnostic imaging* ; HL-60 Cells ; K562 Cells ; Cell Line, Tumor ; U937 Cells

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

Objective:To investigate the prognoses of patients with medial medullary infarction (MMI) or lateral medullary infarction (LMI) and their influencing factors.Methods:A retrospective analysis was performed; 489 patients with acute medullary infarction admitted to Department of Neurology, Tianjin Huanhu Hospital from January 2017 to January 2024 were enrolled. Among them, 186 patients had MMI, which was divided into isolated MMI group ( n=126) and group of MMI with other infarcts ( n=60); 303 patients had LMI, which was divided into isolated LMI group ( n=176) and group of LMI with other infarcts ( n=127). Prognosis 90 days after onset was assessed by modified Rankin Scale (mRS, scores of 3-6 as poor prognosis). Clinical data, prognosis and mortality 90 days after onset, early neurological deterioration, respiratory failure, and complications were compared between isolated MMI group and group of MMI with other infarcts and between isolated LMI group and group of LMI with other infarcts. Univariate and multivariate Logistic regression analyses were used to identify the independent influencing factors for poor prognosis 90 days after onset in patients with MMI or LMI. Results:(1) Compared with isolated MMI group, group of MMI with other infarcts had significantly lower rates of alcohol history and sensory symptoms but higher rates of Horner's syndrome, dysphagia, dysarthria, and facial palsy ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly lower rates of sensory symptoms but higher rates of dizzy and dysarthria, and statistically different Trial of ORG 10172 in Acute Stroke Treatment types ( P<0.05). (2) The poor prognosis rate 90 days after onset in patients with MMI was significantly higher than that in patients with LMI (31.8% vs. 18.8%, P<0.05). Compared with isolated MMI group, group of MMI with other infarcts had significantly higher rates of respiratory failure, urinary retention, and pulmonary infection ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly higher rates of poor prognosis 90 days after onset, mortality 90 days after onset, early neurological deterioration, respiratory failure, stress ulcers, and pulmonary infection ( P<0.05). (3) Multivariate Logistic regression analysis revealed that dyskinesia ( OR=10.522, 95% CI: 1.246-88.853, P=0.031) and vertical multi-level involvement ( OR=4.585, 95% CI: 1.405-14.962, P=0.012) were independent influencing factors for poor prognosis in isolated MMI patients 90 days after onset; age ( OR=1.089, 95% CI: 1.017-1.166, P=0.015), vertical multi-level involvement ( OR=9.429, 95% CI: 1.625-54.502, P=0.012) were independent influencing factors for poor prognosis in MMI patients with other infarcts 90 days after onset; age ( OR=1.069, 95% CI: 1.006-1.136, P=0.031) and vertical multi-level involvement ( OR=7.125, 95% CI: 2.243-22.636, P<0.001) were independent influencing factors for poor prognosis in isolated LMI patients 90 days after onset; diabetes ( OR=2.807, 95% CI: 1.056-7.461, P=0.038), dysphagia ( OR=6.821, 95% CI: 1.978-23.518, P=0.002), and temporal-occipital infarcts ( OR=3.419, 95% CI: 1.133-10.302, P=0.029) were independent influencing factors for poor prognosis in LMI patients with other infarcts. Conclusion:Patients with LMI had better prognosis compared with patients with MMI; however, LMI patients with other infarcts had poorer prognosis compared with LMI patients; LMI patients with diabetes mellitus, dysphagia or temporal-occipital infarcts are prone to have poor prognosis.

BACKGROUND:Overexpression of the nuclear factor I-C gene in vitro promotes the differentiation of human stem cells from apical papilla,as does the activation of the Wnt/β-catenin signaling pathway.Moreover,nuclear factor I-C regulates the Wnt/β-catenin pathway in mesenchymal stem cells.However,whether nuclear factor I-C can affect cell differentiation by activating the Wnt/β-catenin pathway inhuman stem cells from apical papilla has not been reported.OBJECTIVE:To investigate the role of nuclear factor I-C in the Wnt/β-catenin signaling pathway in regulating the differentiation of human stem cells from apical papilla.METHODS:H uman stem cells from apical papilla were cultured by the slide-covered tissue block method and lentiviral transfection overexpressing the nuclear factor I-C gene.(1)A control group,an empty viral vector group,and an overexpressed nuclear factor I-C gene group were set up.The expression ofβ-Catenin,LRP5,and TCF7L2 was detected by Western blotting.(2)The control group,empty viral vector group,overexpressed nuclear factor I-C gene group,and overexpressed nuclear factor I-C gene+DKK-1(Wnt pathway inhibitor)group were set up.Alkaline phosphatase staining and activity quantification were performed after 7 days of osteogenic induction.qPCR and Western blotting were performed to detect the expression of Runt-related transcription factor 2,dentin salivary phosphoprotein,osteocalcin mRNA,and protein after 14 days of osteogenic induction.Alizarin Red staining was used to observe the formation of mineralized nodules.RESULTS AND CONCLUSION:(1)Compared with the control and empty viral vector groups,the expression of Wnt/β-Catenin pathway-related proteins β-Catenin,LRP5,and TCF7L2 inhuman apical dentin papilla stem cells was significantly increased in the overexpressed nuclear factor I-C gene group(P＜0.01).(2)Compared with the control and empty viral vector groups,the expression of alkaline phosphatase and osteocalcin in human apical dentin papilla stem cells was significantly increased(P＜0.01);the expression levels of Runt-related transcription factor 2,dentin salivary phosphoprotein,osteocalcin mRNA and protein were significantly higher(P＜0.01),and the number of mineralized nodules was significantly increased(P＜0.01)in the overexpressed nuclear factor I-C gene group.(3)Compared with the overexpressed nuclear factor I-C gene group,the alkaline phosphatase activity and the expression of Runt-related transcription factor 2,dentin salivary phosphoprotein,osteocalcin mRNA and protein expression levels were significantly down-regulated(P＜0.05),and the number of mineralized nodules was significantly reduced(P＜0.05)in human stem cells from apical papilla of the overexpressed nuclear factor I-C gene+DKK-1 group.The results show that nuclear factor I-C can activate the Wnt/β-catenin signaling pathway in human stem cells from apical papilla and mediate the osteogenic/odontogenic differentiation of human stem cells from apical papilla.

Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)applied to the supplementary motor area(SMA)or primary motor cortex(M1)on upper limb function in stroke patients in terms of motor sequence learning.Methods From April,2024 to February,2025,60 inpatients were recruited from the First Affiliated Hospital with Nan-jing Medical University.They were randomly assigned into the control group,SMA group and M1 group,with 20 patients in each group.All the groups received medication and conventional rehabilitation.On this basis,SMA group underwent HF-rTMS on the affected side's SMA,while M1 group received HF-rTMS on the affected side's M1 for two weeks.All the groups were measured with motor evoked potentials(MEP),the serial reaction time(RT)task,Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Barthel Index(MBI)before and after intervention.Results The SMA and M1 groups dropped one case respectively.MEP elicitation rate of the affected side's increased in SMA and M1 groups(P<0.05),and it was better than that in the control group(χ2>4.792,P<0.05).The intra-group effects of RTsequential sequence,FMA-UE and MBI scores were significant(|F|>81.546,P<0.05).The inter-group effects of RTrandom sequence,RTsequential sequence,?RT,and MBI scores were significant(F>3.228,P<0.05).The in-teractive effects of RTrandom sequence,RTsequential sequence,?RT,FMA-UE and MBI scores were significant(|F|>3.520,P>0.05).After intervention,RTsequential sequence,?RT,FMA-UE and MBI scores improved(P<0.05).RTrandom sequence was lower in SMA group than in the control group(P<0.017),RTsequential sequence,?RT,FMA-UE and MBI scores im-proved more in SMA and M1 groups than in the control group(P<0.05),but no significant difference was found between the SMA group and the M1 group(P>0.05).Conclusion HF-rTMS applied to the affected SMA or M1 can activate motor sequence learning and promote the recov-ery of upper limb function in stroke patients.