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.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective To investigate the achievement of early fluid resuscitation targets and factors influencing 28-day outcomes in patients with sepsis.Methods A retrospective cohort analysis was conducted.A total of 164 patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University between January 2022 and January 2024 were enrolled.Patients were divided into survival and death groups based on 28-day survival status,with both groups receiving early fluid resuscitation.Comparisons were made between groups for general characteristics[gender,age,body mass index(BMI),infection site,comorbidities],primary indicators[central venous pressure(CVP),mean arterial pressure(MAP),urine output],and secondary indicators[blood lactate acid(Lac),procalcitonin(PCT),heart rate,sequential organ failure assessment(SOFA)on intensive care unit(ICU)admission day,Glasgow coma scale(GCS),duration and dose of vasoactive medication use].Univariate analysis identified variables associated with prognosis,followed by multivariate Logistic regression to select independent risk factors.Receiver operator characteristic(ROC curve)were plotted to assess predictive performance of each risk factor for the 28-day prognosis of patients with sepsis.Results This study included 164 patients.The primary infection sites were mainly the lungs,abdominal cavity,and urinary system,accounting for 42.7%(70/164),38.4%(63/164),and 9.1%(15/164)respectively.The survival group comprised 141 patients,while the the death group included 23 patients.No statistically significant differences existed between groups in gender,BMI,infection site(soft tissue infection vs.others),underlying diseases,MAP,urine output(all P>0.05).Compared to the survival group,the death group showed significantly higher age,pulmonary infection rate,Lac levels,vasoactive drug duration/dose,heart rate,and SOFA scores,while the rates of abdominal,and urinary tract infection,as well as CVP,PCT,and GCS scores were significantly lower(all P<0.05).The achievement rates of early fluid resuscitation parameters:MAP target achievement was highest at 78.7%(129/164),followed by urine output compliance at 78.0%(128/164),while CVP compliance was the lowest at 39.0%(64/164).The overall compliance rate was 21.3%(35/164).Univariate analysis showed that age,pulmonary infection,Lac levels,duration and dose of vasoactive drugs,heart rate,PCT,GCS score,and SOFA score were all risk factors affecting the 28-day prognosis of patients with sepsis(all P<0.05).Multivariate Logistic regression analysis showed Lac levels,and pulmonary infection were independent risk factors affecting 28-day prognosis of patients with sepsis[odds ratio(OR)were 0.801,3.966,0.812,95%confidence interval(95%CI)were 0.711-0.903,1.149-13.696,0.674-0.979 respectively,P values were<0.001,0.029,0.029 respectively].ROC curve analysis demonstrated that age,Lac levels,and pulmonary infection all possessed predictive value for 28-day outcomes(all P<0.05).Age exhibited the highest predictive value with an AUC of 0.922.At the optimal cut-off of 76.6 years,sensitivity reached 95.7%and specificity 80.9%.Conclusion The overall achievement rate of early fluid resuscation in sepsis patients was low,with age,Lac levels,and pulmonary infection being major factors influencing poor prognosis.

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.

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.