ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Adverse drug reactions （ADRs） refer to harmful or unintended reactions unrelated to the intended purpose of medication administration， which can lead to various issues such as accelerated disease progression and prolonged hospitalization. Traditional ADRs monitoring systems （such as spontaneous reporting systems） suffer from limitations such as low reporting rates and inconsistent data quality， which hinder the early prevention and control of ADRs. With the rapid development of information technology， machine learning has emerged as a powerful tool for management and decision-making of ADRs by leveraging its strengths in feature extraction and dynamic temporal pattern analysis. By reviewing relevant literature at home and abroad in recent years， this paper summarizes the progress in the application of machine learning for ADRs prediction. It is found that machine learning has gradually been applied to the early warning and risk prediction of ADRs in target organs such as the kidneys， liver， heart and bone marrow （such as acute kidney injury， drug-induced liver injury， and so on）. Although machine learning demonstrates significant application potential in the field of ADRs prediction， it still faces limitations such as inadequate quality control of clinical data， lack of standardized criteria for model performance evaluation， insufficient model interpretability and difficulties in clinical translation. In the future， the development trend of machine learning in the field of ADRs prediction should follow a “technology-validation-integration” pathway to systematically promote the practical implementation of models.

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

Objective: To explore the effects of personality and sleep quality with psychological distress of junior and senior high school stduents, so as to provide a reference basis for precise interventions of junior and senior high school students mental health. Methods: In October 2023, a convenience sampling method was used to select 9 034 students aged 12-17 from Shiyan City as the study subjects. The Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10) were used to collect information on sleep quality and psychological distress of junior and senior high school stduents. Between group comparison was conducted by using t-test and Chi-square test. Generalized linear models were employed to analyze the interaction and joint effects of personality and sleep quality on psychological distress. Results: The generalized linear model analysis showed that the interaction between personality and sleep quality on psychological distress was statistically significant of junior and senior high school students(effect size=0.80, P <0.01). The general linear model analysis indicated that, after adjusting for variables such as age, gender, screen time, and daily sitting time with the extroverted and good sleep quality group as the reference, the introverted and poor sleep quality group had the largest mean difference in psychological distress scores (difference=0.51, P <0.05). When stratified by sleep quality, psychological distress scores were higher in the introverted and neutral personality groups with both poor and good sleep quality compared to the extroverted group (poor sleep quality: introverted difference=3.71, neutral difference=1.14; good sleep quality: introverted difference=2.23, neutral difference=0.57, all P < 0.05). When stratified by personality, psychological distress scores were higher in the poor sleep quality groups for introverted, neutral, and extroverted individuals compared to their good sleep quality counterparts (differences=8.66, 7.83, 7.34, all P < 0.05 ). Conclusions Personality and sleep quality have interactive and joint effects on psychological distress of junior and senior high school stduents. Personalized psychological interventions should be developed based on personality and sleep quality.

ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.