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.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Sishen Pills and its separated prescriptions are classic prescriptions of traditional Chinese medicine to treat intestinal diseases. In this study, a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry(HPLC-ESI-MS/MS) technology was used to identify the components of Sishen Pills, Ershen Pills, and Wuweizi Powder. The positive and negative ion sources of electrospray ionization were simultaneously collected by mass spectrometry. A total of 11 effective components were detected in Sishen Pills, with four effective components detected in Ershen Pills and eight effective components detected in Wuweizi Powder, respectively. To explore the effects of Sishen Pills and its separated prescriptions on the human intestinal flora, an in vitro anaerobic fermentation model was established, and the human intestinal flora was incubated with Sishen Pills, Ershen Pills, and Wuweizi Powder in vitro. The 16S rDNA sequencing technology was used to analyze the changes in the intestinal flora. The results showed that compared with the control group, Sishen Pills, and its separated prescriptions could decrease the intestinal flora abundance and increase the Shannon index after fermentation. The abundance of Bifidobacterium was significantly increased in the Sishen Pills and Ershen Pills groups. However, the abundance of Lactobacillus, Weissella, and Pediococcus was significantly increased in the Wuweizi Powder group. After fermentation for 12 h, the pH of the fermentation solution of three kinds of liquids with feces gradually decreased and was lower than that of the control group. The decreasing amplitude in the Wuweizi Powder group was the most obvious. The single-bacteria fermentation experiments further confirmed that Sishen Pills and Wuweizi Powder had inhibitory effects on Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis, and the antibacterial activity of Wuweizi Powder was stronger than that of Sishen Pills. Both Sishen Pills and Ershen Pills could promote the growth of Lactobacillus brevis, and Ershen Pills could promote the growth of Bifidobacterium adolescentis. This study provided a more sufficient theoretical basis for the clinical application of Sishen Pills and its separated prescriptions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/chemistry* ; Fermentation/drug effects* ; Bacteria/drug effects* ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Intestines/microbiology*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

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: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging