ObjectiveTo investigate the effects of salidroside （SAL） on the impaired bioactivity of endothelial progenitor cells （EPCs） in atherosclerotic （As） mice and the potential mechanisms regarding AMP-activated protein kinase （AMPK）. MethodsAtherosclerosis was induced in 8-week-old male ApoE^-/- mice with high-fat diet. Intragastric administration of SAL was given to one mice group to investigate the effects of SAL on aortic plaque burden， plasma NO level， the migration and angiogenic capabilities of bone marrow-derived EPCs （BM-EPCs）. The proliferation， migration and vasculogenic properties of EPCs isolated from As mice were investigated in vitro. AMPK-sh-RNA or the AMPK inhibitor Compound C was used to investigate the role of AMPK/Akt/eNOS pathway in the regulatory effects of SAL. ResultsCompared with As group， NO level was significantly elevated in SAL group. The sizes of atherosclerotic plaques at the aortic root were reduced with smaller lipid cores in SAL group compared with As group. Moreover， the migration and angiogenesis capacity of EPCs markedly decreased in As mice， while SAL treatment reversed these impairments. Incubation with SAL at concentrations of 20， 40， and 80 μmol/L for 48 hours significantly promoted the proliferation， migration， and angiogenesis of EPCs. AMPK-sh-RNA transfection abrogated the 20 μmol/L SAL improvement in EPC biological activities. Western blot analysis further demonstrated that treatment with Compound C blocked the activation of AMPK/Akt/eNOS signaling pathway induced by SAL. ConclusionSAL upregulates the biological functions of EPCs through activating the AMPK/Akt/eNOS signaling pathway， thereby ameliorating EPC dysfunction during the pathological progression of atherosclerosis.

Objective: To investigate the cross sectional association between bedroom nocturnal light exposure and objectively measured sleep parameters in college students, so as to provide evidence for promoting sleep health. Methods: From September to October 2019, a convenience sampling method was used to recruit 365 healthy college students from two universities in Hefei, establishing a cohort. Bedroom nocturnal light exposure was measured at the individual level for two consecutive days using a portable illuminometer (TES-1339R; Taishi Corp, Taiwan, China). Sleep parameters were objectively measured over seven consecutive days using wrist worn accelerometers (ActiGraph GT3X-BT, Pensacola, FL). Multiple linear regression models were employed to examine the association between nocturnal light exposure and sleep parameters. Results: Compared to the low nocturnal light exposure (<3 lx) group, the high exposure (≥3 lx) group exhibited significantly lower sleep efficiency[(93.5± 2.7 )%,(92.2±2.9)%, t =3.93], longer wake after sleep onset (WASO)[(24.7±90.3)(29.2±11.2)min, t =-3.66], higher movement index(11.0±3.6, 12.2± 3.8, t =-2.80), and higher sleep fragmentation index(20.5±6.5,23.0±7.0, t =-3.24) (all P <0.01). After adjusting for covariates,multiple linear regression showed that,compared to the low nocturnal light exposure group, the high exposure group had reduced sleep efficiency ( β =-1.15, 95% CI =-1.78 to -0.52), increased WASO [ β (95% CI )=3.94(1.55- 6.33 )], higher movement index[ β (95% CI )=1.05(0.20-1.89)], and elevated sleep fragmentation index[ β (95% CI )=2.35(0.81-3.88)](all P <0.05). Conclusions Light exposure at night negatively impacts college students sleep. Optimizing bedroom lighting management may improve sleep quality in adolescents.

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.

According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*