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.

Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Inteins are unique protein insertion sequences capable of self-excision, enabling the covalent ligation of flanking extein peptides via amide bond formation. This process proceeds spontaneously without requiring external enzymes, cofactors, or chemical reagents, granting inteins exceptional biocompatibility and traceless performance in protein engineering applications. Split inteins represent a specialized and versatile subclass whose splicing domains are encoded by two separate gene fragments rather than a single continuous open reading frame. These fragments, known as the N-terminal (IntN) and C-terminal (IntC) split inteins, associate through non-covalent interactions including hydrophobic forces, hydrogen bonds, and van der Waals forces to assemble into an active three-dimensional structure, which then drives efficient extein ligation and enables protein trans-splicing. Protein trans-splicing mediated by split inteins has become a cornerstone for traceless protein ligation owing to its high specificity and irreversibility, fundamentally reshaping strategies for protein modification, assembly, and functional regulation. Compared with traditional chemical ligation methods, split intein systems require no complex chemical derivatization of peptide fragments and can operate efficiently at micromolar concentrations under physiological conditions, thus avoiding structural and functional damage caused by organic reagents. In contrast to enzymatic ligation tools such as sortase, split inteins eliminate the need for additional enzymes or cofactors, simplifying reaction systems, reducing costs, and minimizing non-specific side products. These distinctive advantages render split inteins highly promising for applications in chemical biology, synthetic biology, and biopharmaceutical development. In recent years, deepened mechanistic understanding has established structure-guided rational design as the primary approach to overcoming key limitations of split inteins, including intrinsic aggregation propensity, strict extein sequence dependence, and limited splicing efficiency. Bioinformatic tools have been used to identify aggregation-prone regions in the IntN fragment, and site-directed mutagenesis of hydrophobic residues, relocation of split sites, or removal of misfolding-prone sequences has substantially reduced in vitro aggregation and improved soluble expression and assembly activity. Rational engineering of catalytic residues and adjacent flexible loops has relaxed strict amino acid preferences at extein junctions, enhancing sequence tolerance and reducing the risk of functional impairment in target proteins. Consensus design based on multiple sequence alignments has yielded ultra-fast splicing variants such as Cfa DnaE and Cat-TerL, which exhibit significantly accelerated kinetics and improved tolerance to denaturing conditions. Meanwhile, advances in structural biology have further clarified the conformational dynamics and catalytic mechanisms of splicing, supporting the precise design of high-performance intein modules. On this basis, electrostatic interaction tuning and metagenomic screening have yielded multiple mutually orthogonal split intein pairs, enabling selective multi-fragment protein ligation and providing new routes for the efficient synthesis of large multi-domain functional proteins. With these engineered split inteins offering continuously improved performance and expanded applicability, protein trans-splicing has been widely applied in numerous cutting-edge areas of protein research and biomedicine. In gene delivery, split intein-based systems overcome the packaging limit of adeno-associated viral vectors, enabling the accurate reconstitution of large therapeutic proteins and base editors in target cells, thereby enhancing the efficacy and scope of gene therapy for genetic diseases. In internal protein sequence editing, split inteins mediate precise sequence replacement and modification in flexible regions or loops of target proteins, without the need for complex multi-step ligation and protein refolding involved in traditional protein semisynthesis. In protein-protein interaction studies, intein-mediated splicing covalently captures transient and weak intracellular complexes, enabling sensitive, high-throughput interaction detection and drug screening. In synthetic biology, conditionally controllable splicing systems support the construction of diverse intracellular and cell-surface biological logic gates for the precise regulation of cellular behavior. In mechanistic biochemical research, split inteins enable photocatalytic proximity labeling and site-specific tagging, allowing the preparation of homogeneous protein samples carrying precise post-translational modifications such as ubiquitination and polyglutamylation for chromatin interactome analysis and epigenetic studies. Moreover, covalent trapping strategies using split inteins stabilize transient enzymatic intermediates, providing unprecedented insights into molecular mechanisms such as nucleosome ubiquitination that are difficult to elucidate using conventional methods. This review systematically summarizes key technological advances in split inteins over the past decade, highlighting engineering strategies, mechanistic insights, and the development of orthogonal components. It comprehensively surveys emerging applications at the frontiers of protein research, analyzes current core challenges, and proposes future directions, particularly emphasizing artificial intelligence-driven de novo design and novel splicing pathways to break existing technical bottlenecks. By enabling traceless, efficient, and versatile protein manipulation, split inteins continue to serve as indispensable tools that drive innovation in protein engineering and fundamental life science research.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

Objective To explore the mechanism of Shen Hong capsule in preventing and treating acute mountain sickness based on biological information platform and in vitro experiment. Methods Traditional Chinese Medicine Systems Pharmacology （TCMSP） and Traditional Chinese Medicine Information Database （TCMID） were used to obtain the active components and predicted targets of Shen Hong capsule. Therapeutic Target Database （TTD）, Disease Gene Network （DisGeNET） database and GeneCards database were used to search for the targets of acute mountain sickness related diseases, and the potential therapeutic targets were obtained. The protein-protein interaction （PPI） was analyzed by Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）, the Database for Annotation, Visualization, and Integrated Discovery （DAVID） online platform was used to analyse the Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG） signal pathway enrichment. The network information was visualized by Cytoscape software, the key targets in PPI network were obtained according to the topology data, and the binding ability of main active components and key therapeutic targets were analyzed by molecular docking. The validation of the main active components was performed by liquid chromatography-mass spectrometry （LC-MS）. The hypoxia model was created by H9c2 cells, apoptosis was visualized by Hoechst33342 staining, and key target proteins were verified by Western blot. Results 91 active components, 3 main active components and 150 predicted targets were selected from Shen Hong capsule. 515 targets of altitude sickness-related diseases and 37 targets of Shen Hong capsule regulating altitude sickness-related diseases were screened out. 44 related signal pathways, such as HIF-1 signal pathway, PPAR signal pathway, drug metabolism - cytochrome P450, were enriched and analyzed. TNF, IL1B, VEGFA, NOS3, EGFR, ESR1, PPARG, NR3C1, HMOX1 and IFNG were 10 key targets. The molecular docking results showed that the docking conformations between the main active components and the key targets were stable. The three main active components of quercetin, luteolin and kaempferol were identified by LC-MS, and in vitro experiments proved that Shen Hong capsule could relieve acute hypoxia injury by regulating the expression of HIF-1α, PPARG, NOS3, and TNF. Conclusion Shen Hong capsule could regulate the body’s hypoxia response and metabolism through multi-component, multi-target and multi-channel ways, so as to prevent and treat acute mountain sickness. This study provided a direction for further exploring the mechanism of Shen Hong capsule, and also provided a theoretical basis for further development and clinical application.

ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group， ferroptosis inhibitor group （2 mg·kg^-1）， enalapril group （2.1 mg·kg^-1）， and low- and high-dose （4 g·kg^-1 and 8 g·kg^-1， respectively） Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma， with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment， echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， transforming growth factor-β （TGF-β）， and myosin heavy chain-β （MHC-β） were measured by enzyme-linked immunosorbent assay （ELISA）. Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde （MDA） and glutathione （GSH） in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E₂-related factor 2 （Nrf2） in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. ResultsCompared with the sham group， the model group showed increased left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， disarrangement of myocardial cells， inflammatory cell infiltration， severe myocardial fibrosis， increased myocardial iron deposition， and irregular mitochondrial morphology with vacuolation. Furthermore， the modeling led to increased MDA （P<0.01）， decreased GSH （P<0.01）， diminished Nrf2 fluorescence intensity in the myocardial tissue， and downregulated expression levels of Nrf2， SLC7A11， and GPX4 （P<0.01）. Compared with the model group， Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD， LVESD， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.05， P<0.01）， alleviated pathological changes such as myocardial cell disarrangement， inflammatory cell infiltration， myocardial fibrosis， and iron deposition， lowered the level of MDA （P<0.05， P<0.01）， raised the level of GSH （P<0.05， P<0.01）， improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue， enhanced Nrf2 fluorescence intensity， and upregulated the expression levels of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis， the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group， ferroptosis inhibitor group （2 mg·kg^-1）， enalapril group （2.1 mg·kg^-1）， and low- and high-dose （4 g·kg^-1 and 8 g·kg^-1， respectively） Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma， with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment， echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， transforming growth factor-β （TGF-β）， and myosin heavy chain-β （MHC-β） were measured by enzyme-linked immunosorbent assay （ELISA）. Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde （MDA） and glutathione （GSH） in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E₂-related factor 2 （Nrf2） in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. ResultsCompared with the sham group， the model group showed increased left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， disarrangement of myocardial cells， inflammatory cell infiltration， severe myocardial fibrosis， increased myocardial iron deposition， and irregular mitochondrial morphology with vacuolation. Furthermore， the modeling led to increased MDA （P<0.01）， decreased GSH （P<0.01）， diminished Nrf2 fluorescence intensity in the myocardial tissue， and downregulated expression levels of Nrf2， SLC7A11， and GPX4 （P<0.01）. Compared with the model group， Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD， LVESD， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.05， P<0.01）， alleviated pathological changes such as myocardial cell disarrangement， inflammatory cell infiltration， myocardial fibrosis， and iron deposition， lowered the level of MDA （P<0.05， P<0.01）， raised the level of GSH （P<0.05， P<0.01）， improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue， enhanced Nrf2 fluorescence intensity， and upregulated the expression levels of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis， the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.

This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

The main active compound, 3,4-dihydroxyacetophenone(3,4-DHAP), in the leaves of Ilex pubescens var. glaber, exhibits various pharmacological activities, including vasodilation and heart protection. Currently, natural extraction and chemical synthesis are the primary methods for obtaining 3,4-DHAP, but both approaches have inherent challenges. To address these problems, this study explored the whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol to 3,4-DHAP using recombinant Escherichia coli, cultivated in a green, cost-effective medium at room temperature and atmospheric pressure. Firstly, this study successfully constructed recombinant E. coli S1, which contained only the HpaBC gene, and recombinant E. coli S3, which contained both the Hped and HpaBC genes. The ability of S1 and S3 to synthesize 3,4-DHAP from their respective substrates was then evaluated through whole-cell bioconversion. Based on these results, the effects of four factors, i.e., substrate concentration, IPTG concentration, induction temperature, and transformation temperature, on the whole-cell bioconversion yield of S3 were investigated using an orthogonal experiment. The results showed that the factors influenced the yield in the following order: transformation temperature > induction temperature > IPTG concentration > substrate concentration. The optimal conditions were found to be a transformation temperature of 35 ℃, IPTG concentration of 0.1 mmol·L~(-1), induction temperature of 25 ℃, and substrate concentration of 10 mmol·L~(-1). Finally, the effect of transformation time on the yield of 3,4-DHAP was further examined under the optimal conditions. The results indicated that as the transformation time increased, the yield of 3,4-DHAP steadily increased. The highest yield of 260 mg·L~(-1) with a productivity of 17% was achieved after 72 hours of transformation. In conclusion, this study successfully achieved the whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol to 3,4-DHAP using recombinant E. coli for the first time, laying the groundwork for further optimization and development of the biosynthesis of 3,4-DHAP.
Escherichia coli/genetics* ; Acetophenones/chemistry* ; Ethanol/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Biotransformation