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.

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.

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.

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.

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.

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.