Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

Objective To analyze the correlation between cardiac function and degree of coronary artery lesion in elderly patients with coronary heart disease. Methods A total of 110 elderly patients with coronary heart disease and 30 elderly people without coronary heart disease (non-coronary heart disease group) in the Third People's Hospital of Chengdu were selected for the study. Based on Gensini score, the patients with coronary heart disease were classified into mild, moderate and severe lesion groups. The echocardiographic indicators and myocardial injury indicators [cardiac troponin I (cTnI), creatine kinase (CK), creatine kinase isoenzyme (CK-MB)] were compared among the groups. The correlation between cardiac function indicators and degree of coronary artery lesion and the evaluation value of various indicators on severe coronary artery lesion were analyzed. Results The left ventricular ejection fraction (LVEF) was represented as severe lesion groupmoderate lesion group>mild lesion group> non-coronary heart disease group (P<0.05). LVEF showed a negative correlation with degree of coronary artery lesion (P<0.05), while LVEDD, LVESD, cTnI, CK and CK-MB all exhibited positive correlations with degree of coronary artery lesion (P<0.05). The combined detection of the above indicators demonstrated superior evaluation efficiency on severe coronary artery lesion compared to any single indicator (P<0.05). Conclusion There is a significant correlation between cardiac function and degree of coronary artery lesion in elderly patients with coronary heart disease. Comprehensive evaluation of these indicators is conducive to clinical disease risk stratification and individualized treatment.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

ObjectiveTo explore the mechanism of action of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma in the treatment of recurrent spontaneous abortion （RSA） through network pharmacology， molecular docking， and cell experiment verification. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and UniPort databases were used to screen and organize the active ingredients and corresponding targets of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma. The potential therapeutic targets of RSA were screened in Online Mendelian Inheritance in Man （OMIM）， GeneCards database， DrugBank database， DisGeNET database， and Therapeutic Target Database （TTD）. The potential core targets of Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma for treating RSA were further screened by constructing a protein-protein interaction （PPI） network and topological analysis. Meanwhile， the Database for Annotation， Visualization and Integrated Discovery （DAVID） was chosen to perform enrichment analysis on intersection targets. On this basis， AutoDock software was used for molecular docking， and the data were imported into PyMOL software for visualization and composition. Finally， the cell counting kit-8 （CCK-8） experiment， Transwell cell invasion assay， and Western blot were used to detect the effects of serum containing Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma on HTR-8/SVneo cells and observe the effects on the interleukin （IL）-6/signal transducer and activator of transcription 3（STAT3） signaling pathway and related proteins. ResultsThrough network pharmacology analysis， a total of 69 active ingredients， 73 potential therapeutic targets， and 17 core targets， including IL-6， IL-10， and STAT3， were collected. The 73 common targets were enriched in 614 Gene Ontology （GO） entries and 57 Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways. The molecular docking results indicated that IL-6 and STAT3 had good binding ability with the main active ingredients， including matrine， cryptotanshinone， and tanshinone Ⅱ_A. The cell experiment results showed that， compared with those of the control group， after 24 hours of treatment with the drug-containing serum， the survival and invasion rates of HTR-8/SVneo cells were significantly increased （P<0.05）， and the expression of IL-6/STAT3 signaling pathway and related proteins IL-10 and c-Myc was significantly elevated （P<0.05）. Moreover， the trend of action in the drug-containing serum group was consistent with that of pathway agonists. ConclusionCuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma may enhance the survival rate and invasive activity of HTR-8/SVneo cells to further prevent and treat RSA by activating the IL-6/STAT3 signaling pathway and upregulating the expression of downstream factors IL-10 and c-Myc in the pathway.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.