ObjectiveBased on whole-animal mass spectrometry imaging technology， spatial metabolomics was used to characterize in situ the metabolic alteration patterns in the lungs and brain of a rat model of lung heat-induced cough and asthma， as well as after treatment with Xiebai San. MethodsNine Sprague-Dawley （SD） rats were randomly divided into a blank group （physiological saline）， a model group （physiological saline）， and a Xiebai San group （9 g·kg^-1）， with three rats in each group. The model group and the Xiebai San group were both induced using lipopolysaccharide-ovalbumin （LPS-OVA） to establish an asthma rat model. After treatment with Xiebai San， the animals were euthanized on day 21 and rapidly frozen in liquid nitrogen to preserve morphology. Whole-animal tissue sections were prepared using a cryomicrotome， and imaging was performed using the Air-flow-assisted Desorption Electrospray Ionization Mass Spectrometry Imaging （AFADESI-MSI） platform. Based on the corresponding optical images， ion data of metabolites from the lung and brain tissues of each group were extracted. Differential metabolites were analyzed using SIMCA and GraphPad Prism 9.0 software. Metabolites were identified using the HMDB （https：//hmdb.ca/） and LipidMAPS^® （https：//www.lipidmaps.org/） databases， and metabolic changes in the lungs and brain were analyzed. ResultsMass spectrometry imaging showed that， after Xiebai San intervention， components such as neoglycyrrhizin and glycyrrhizin from Glycyrrhizae Radix et Rhizoma， as well as palmitamide from Lycii Cortex， were significantly distributed in the lung and brain tissues of rats. Lung analysis indicated that substances with anti-inflammatory effects， such as citric acid， were significantly decreased （P0.01）， while lipid metabolites such as lysophosphatidylethanolamine （LPE 17：1）， LPE （22：4）， and LPE （19：0） （P0.01） were significantly increased， showing a marked inflammatory response in the model group. After Xiebai San intervention， these conditions were notably improved. Analysis of metabolic changes in brain tissue showed that， compared with the blank group， amino acid and fatty acid metabolic pathways in the model group exhibited restricted alterations. Among them， levels of aspartic acid， glutamic acid， fatty acid （FA 18：5）， hydroxy fatty acids （FAHFA 36：0；O）， FA （6：1；O6）， and LPE （18：1） increased， whereas FA （16：0） and FA （20：4） significantly decreased. Administration of Xiebai San improved these metabolic abnormalities in the brain. Systematic analysis of lung and brain metabolic changes in rats with lung heat-induced cough and asthma showed that antioxidant unsaturated phospholipid substances were significantly decreased in the model group， suggesting oxidative stress and inflammation-related lung-brain axis responses after the onset of lung heat-induced cough and asthma. ConclusionUsing whole-animal mass spectrometry imaging combined with spatial metabolomics revealed the in vivo distribution of Xiebai San constituents， characterized the metabolic alterations in the lungs and brain caused by lung heat-induced cough and asthma， and systematically demonstrated the lung-brain axis inflammatory responses and the regulatory effects of Xiebai San. These findings provide valuable information for the study of Chinese medicine in lung heat-induced cough and asthma.

ObjectiveBased on whole-animal mass spectrometry imaging technology， spatial metabolomics was used to characterize in situ the metabolic alteration patterns in the lungs and brain of a rat model of lung heat-induced cough and asthma， as well as after treatment with Xiebai San. MethodsNine Sprague-Dawley （SD） rats were randomly divided into a blank group （physiological saline）， a model group （physiological saline）， and a Xiebai San group （9 g·kg^-1）， with three rats in each group. The model group and the Xiebai San group were both induced using lipopolysaccharide-ovalbumin （LPS-OVA） to establish an asthma rat model. After treatment with Xiebai San， the animals were euthanized on day 21 and rapidly frozen in liquid nitrogen to preserve morphology. Whole-animal tissue sections were prepared using a cryomicrotome， and imaging was performed using the Air-flow-assisted Desorption Electrospray Ionization Mass Spectrometry Imaging （AFADESI-MSI） platform. Based on the corresponding optical images， ion data of metabolites from the lung and brain tissues of each group were extracted. Differential metabolites were analyzed using SIMCA and GraphPad Prism 9.0 software. Metabolites were identified using the HMDB （https：//hmdb.ca/） and LipidMAPS^® （https：//www.lipidmaps.org/） databases， and metabolic changes in the lungs and brain were analyzed. ResultsMass spectrometry imaging showed that， after Xiebai San intervention， components such as neoglycyrrhizin and glycyrrhizin from Glycyrrhizae Radix et Rhizoma， as well as palmitamide from Lycii Cortex， were significantly distributed in the lung and brain tissues of rats. Lung analysis indicated that substances with anti-inflammatory effects， such as citric acid， were significantly decreased （P0.01）， while lipid metabolites such as lysophosphatidylethanolamine （LPE 17：1）， LPE （22：4）， and LPE （19：0） （P0.01） were significantly increased， showing a marked inflammatory response in the model group. After Xiebai San intervention， these conditions were notably improved. Analysis of metabolic changes in brain tissue showed that， compared with the blank group， amino acid and fatty acid metabolic pathways in the model group exhibited restricted alterations. Among them， levels of aspartic acid， glutamic acid， fatty acid （FA 18：5）， hydroxy fatty acids （FAHFA 36：0；O）， FA （6：1；O6）， and LPE （18：1） increased， whereas FA （16：0） and FA （20：4） significantly decreased. Administration of Xiebai San improved these metabolic abnormalities in the brain. Systematic analysis of lung and brain metabolic changes in rats with lung heat-induced cough and asthma showed that antioxidant unsaturated phospholipid substances were significantly decreased in the model group， suggesting oxidative stress and inflammation-related lung-brain axis responses after the onset of lung heat-induced cough and asthma. ConclusionUsing whole-animal mass spectrometry imaging combined with spatial metabolomics revealed the in vivo distribution of Xiebai San constituents， characterized the metabolic alterations in the lungs and brain caused by lung heat-induced cough and asthma， and systematically demonstrated the lung-brain axis inflammatory responses and the regulatory effects of Xiebai San. These findings provide valuable information for the study of Chinese medicine in lung heat-induced cough and asthma.

The scientific connotation of the material basis of traditional Chinese medicine （TCM） depends not only on the composition and abundance of its constituents， but more critically on their spatial distribution within medicinal materials and in vivo. However， conventional analytical approaches have limited capacity to resolve in situ spatial information， failing to delve into therapeutic mechanisms of complex TCM systems. Mass spectrometry imaging （MSI） enables label-free in situ analysis with spatial visualization of multiple constituents， providing essential technical support for investigations into the material basis of TCM. In recent years， the application of MSI has continuously expanded across studies of single medicinal materials， processing， compound preparations， and in vivo distribution， systematically elucidating microscale spatial distribution patterns of TCM constituents. Accumulating evidence indicates that MSI facilitates clarification of the relationships among endogenous constituents， biosynthetic pathways， medicinal parts， and geo-authenticity （Daodi）. Moreover， MSI can dynamically depict spatiotemporal transformation of constituents during processing， offering intuitive evidence for the mechanisms underlying toxicity reduction and efficacy enhancement. In the studies of compound preparations， MSI can resolve microregional distribution characteristics of diverse constituents and their potential interactions， thereby deepening the understanding of compatibility principles. In addition， MSI demonstrates unique advantages in in situ tracing of constituents in vivo， as well as in spatially informed quality evaluation and authentication/adulteration identification. Overall， MSI is driving a shift in the research on the material basis of TCM from conventional compositional profiling toward spatial-functional elucidation， providing important technical support for establishing "material-space-efficacy" relationships. Despite remaining challenges in quantification， spatial resolution， and data processing， MSI shows broad promise for application in modern TCM research.

OBJECTIVE To explore the potential mechanisms and bioactive compounds of licorice against COVID-19 based on a multidimensional interaction of"component-disease-symptom-target".METHODS Firstly,candidate target sets for licorice compo-nents were obtained from the ETCM2.0 database based on the Encyclopedia of Traditional Chinese Medicine,and the disease symp-toms and associated target sets for COVID-19 were derived from the GeneCards and HPO databases.And then a protein interaction network was constructed using the String database(version 12.0).By calculating topological eigenvalues and functional enrichment analysis,the potential mechanisms of action were explored.Combined with Schr?dinger molecular docking virtual screening,candidate pharmacodynamic substances were identified.Fluorescence resonance energy transfer was used for experimental verification.RESULTS Licorice might improve symptoms of COVID-19(fever,chest pain and so on)by regulating the imbalance of"immune-inflammation"network and signal transduction abnormalities during the development and progress of COVID-19,such as coronavirus disease-COVID-19,Toll-like receptor signaling pathway and NOD-like receptor signaling pathway.The components,such as Isos-chaftoside and Hesperidin,were identified to possess high binding affinity with the critical enzymes for viral replication.Isoschaftoside,Hesperidin,Isoliquiritin apioside and Vicenin-2 exhibited varying degrees of inhibition on the enzyme of 3CLpro at different concentra-tions while excluding the interference of the compounds' fluorescence.CONCLUSION Through experimental verification using a multidimensional interaction network of"component-disease-symptom-target",the key pharmacologically active substances of licorice in the fight against COVID-19 are preliminarily identified,and their mechanism of action through overall regulation is elucidated.

Objective To analyze the effects of different traction sites and directions on the maxilla and upper dentition when using clear aligners combined with protraction for the treatment of maxillary deficiency.Methods A three-dimensional(3D)finite element model including the zygomaticomaxillary complex,maxillary dentition,and clear aligners was constructed.The models were divided into Group 1(traction hook at the distal of the lateral incisor)and Group 2(traction hook at the distal of the canine).Each group was analyzed under four loading conditions with protraction angles of 0°,10°,20°,and 30° relative to the occlusal plane.A unilateral protraction force of 500 g was applied.The differences in stress distribution and displacement of the maxillary bone and dentition under different loading conditions were analyzed.Results When the protraction angle was 30°,both groups showed forward and downward displacement of the maxilla,while other angles resulted in counterclockwise rotation.Under the same protraction direction,the total displacement of the maxilla and displacements in all directions in Group 2 were greater than those in Group 1.The upper central incisors in Group 1 showed lingual displacement,which increased with the protraction angle.The maxillary dentition in Group 2 showed forward displacement,with the minimum total and sagittal displacements at a protraction angle of 30°.Stress concentration was mainly observed in the zygomaticomaxillary suture and anterior alveolar bone regions in both groups,decreasing as the protraction angle increased.Conclusions Clear aligners combined with protraction can be applied to skeletal Class Ⅲ patients with mild maxillary deficiency.When the protraction site is located at the distal of the canine with a 30° downward and forward angle to the occlusal plane,the maxilla can achieve ideal forward and downward displacement with the minimum labial movement of the upper anterior teeth.

BACKGROUND:Osteoporosis is defined as a chronic metabolic bone disease,and a large amount of evidence has shown that gut microbiota is involved in osteoporosis.However,the causal relationship between gut microbiota and osteoporosis is yet unclear.OBJECTIVE:To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.METHODS:Pooled statistics from the MiBioGen Consortium's Genome-Wide Association Analysis(GWAS)of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used.Inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis.Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.RESULTS AND CONCLUSION:The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis.Among them,the R7 genus of Christensenaceae(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028),Coprococus 3(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)and Trichospirillum(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003)may be protective factors for osteoporosis,while Hotella(MR Egger:β=0.006;IVW:β=0.002,P=0.033)and Eubacterium oxyoxide(MR Egger:β=0.001;IVW:β=0.003,P=0.046)may be potential risk factors for osteoporosis.Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis,while R7 of Christensenaceae,Coprococcus 3 and Spirillum can reduce the risk of osteoporosis.Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups.

To investigate the awareness of cognitive impairment disorders among residents of the Xizang Autonomous Region and its influencing factors, thereby providing a basis for targeted prevention and treatment efforts.

Objective To explore the application value of artificial intelligence in medical research assistance, and analyze the key paths to achieve precise execution of model instructions, improvement of model interpretation completeness, and control of hallucinations. Methods Taking esophageal cancer research as the scenario, five types of literature including research articles, case reports, reviews, editorials, and guidelines were selected for model interpretation tests. The model performance was systematically evaluated from five dimensions: recognition accuracy, format accuracy, instruction execution accuracy, content reliability rate, and content completeness index. The performance differences of Ruibin Agent, GPT-4o, Claude 3.7 Sonnet, DeepSeek V3, and DouBao-pro models in medical literature interpretation tasks were compared. Results A total of 15 studies were included, with 3 studies of each type. The five models collectively conducted 1 875 tests. Due to the poor recognition accuracy of the editorial type, the overall recognition accuracy of Ruibin Agent was significantly lower than other models (92.0% vs. 100.0%, P＜0.001). In terms of format accuracy, Ruibin Agent was significantly better than Claude 3.7 Sonnet (98.7% vs. 92.0%, P=0.002) and GPT-4o (98.7% vs. 78.9%, P＜0.001). In terms of instruction execution accuracy, Ruibin Agent was better than GPT-4o (97.3% vs. 80.0%, P＜0.001). In terms of content reliability rate, Ruibin Agent was significantly lower than Claude 3.7 Sonnet (84.0% vs. 92.0%, P=0.010) and DeepSeek V3 (84.0% vs. 94.7%, P＜0.001). In terms of content completeness index, the median scores of Ruibin Agent, GPT-4o, Claude 3.7 Sonnet, DeepSeek V3, and DouBao-pro were 0.71, 0.60, 0.85, 0.74, and 0.77, respectively. Conclusion Ruibin Agent has significant advantages in terms of formatted interpretation of medical literature and instruction execution accuracy. In the future, it is necessary to focus on optimizing the recognition ability of editorial types, strengthening the coverage ability of core elements of various types of literature to improve interpretation completeness, and improving content reliability through optimizing the confidence mechanism to ensure the rigor of medical literature interpretation.

OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Objective To investigate the current status of multidisciplinary team (MDT) approaches in lung cancer management in China to provide a basis for the further promotion and enhancement of the MDT model. Methods From April 2023 to November 2023, physicians engaged in the clinical diagnosis and treatment of lung cancer were selected as the research objects. Questionnaires were distributed online and offline to investigate the cognition of MDT mode, MDT operating mode of their hospital, challenges faced, and direction of improvement. Descriptive analysis was conducted on the survey results. Results A total of 1137 questionnaires were collected, covering 816 general and cancer hospitals in 31 provinces and cities across the country. A total of 88.1% of doctors believe that the current MDT model is feasible, effective, and is of great value in benefiting patients’ survival, improving diagnosis and treatment efficiency, promoting diagnosis and treatment level and standardization, and increasing clinical research enrollment. Meanwhile, 83.5% of doctors state that their hospital has established an MDT team, including a chair and a coordinator, to ensure the smooth operation of the MDT and follow-up. The frequency of MDT is low and the time is long, usually 1–2 times a month and more than 30 minutes discussion time for each case. In addition, 50.1% of doctors indicate MDT cases account for less than 25% of annual diagnosis and treatment cases. Time coordination challenges and lack of administrative support and incentives are the difficulties affecting the operation of MDT. Having well-defined patient criteria is frequently cited as a key area for optimization that could remarkably enhance MDT efficiency. Conclusion After more than a decade of exploration and practice, the MDT model for lung cancer in China has been widely promoted and applied. Optimizing the selection, diagnosis, and treatment of MDT cases and providing administrative support and incentives are the key to enhancing the efficiency of MDT and expanding their benefits to a great number of patients with cancer.