ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Zhibitai Capsules are characterized by their ability to regulate blood lipids, prevent cardiovascular diseases, and protect the liver, making them widely used in clinical practice. When combined with low-dose statins for the treatment of coronary artery disease, their lipid-lowering effect is comparable to that of high-dose statins, while exhibiting a lower incidence of adverse reactions. Therefore, this study reviews the drug components, mechanisms of action, clinical applications, adverse reactions, and safety of Zhibitai Capsules, providing theoretical support for their clinical use in lipid regulation.

The use of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and have improved the survival outcomes of advanced patients while offering better overall safety compared to chemotherapy.However, due to immune senescence, the efficacy and safety of immunotherapy in elderly patients are different from those in non-elderly patients.Moreover, most clinical trials have limited data on elderly patients, and immunotherapy in the elderly population lacks high-level evidence-based medical support.This article introduces the theoretical basis of immunotherapy in the elderly population, summarizes clinical data on the efficacy and safety of immunotherapy for advanced NSCLC in the elderly, and analyses the immunotherapy for special subgroups of elderly patients, aiming to provide a reference basis for treating this population.The results showed that single-agent immunotherapy had good efficacy and safety in elderly patients with advanced NSCLC in the age group of 65-74 years, obtaining long-term survival benefits, However, the benefits of immunotherapy in the elderly population ≥75 years old remian unclear, and the outcomes of immunotherapy in the elderly ≥80 years old were poor.In addition, the performance status (PS) score of ≥2 was a significant factor in reducing the efficacy of single-agent immunotherapy in elderly patients.In addition, a pre-treatment PS score of ≥2 was an independent risk factor for reducing the efficacy of immunotherapy alone.Immunotherapy in combination with chemotherapy in the elderly has shown efficacy comparable to the overall population.However, there is an increased incidence of treatment-related adverse events(TRAEs)in patients ≥75 years of age.Dual-immunity combination therapies are not currently recommended for the treatment of advanced NSCLC in the elderly.Elderly patients with brain metastases have poor prognosis, and treatment may consider ICIs in combination with local radiotherapy.Basic research on how to improve the benefit of immunotherapy in elderly patients is also ongoing.In conclusion, the therapeutic prospect of immunotherapy in advanced NSCLC in the elderly is promising, and more exploration is needed in the future.

Objective: To explore the mechanism of action of Zangjiangzhi capsule (ZJZC) in treating hyperlipidemia (HLP). Methods: The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS/MS). Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment. The SwissTargetPrediction database was used to predict compound targets, and GeneCards, DisGeNet, OMIM, and DRUGBANK databases were used to identify HLP-related targets. Protein–protein interaction diagrams were constructed using the STRING database. The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The “herb-ingredient-target” network was visualized using Cytoscape. Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay. Results: Ninety compounds were identified in ZJZC, including 34 flavonoids, 12 phenols, 10 terpenoids, 10 alkaloids, 8 organic acids, 8 anthraquinones, and 9 other compounds. In total, 904 targets were identified for these compounds. Among them, 158 targets intersected with the HLP target network. Network pharmacology analysis showed that MAPK1, PPAR-α, RXRA, HSP90AA1, PIK3R1, AKT1, PIK3CA, IL6, TNF, and ESR1 are the key targets of action. KEGG enrichment analysis identified 164 pathways. Among these, the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis pathways, regulation of lipids in adipocytes, and insulin resistance are related to HLP. Molecular docking showed good affinity between the key targets and ingredients. Further, ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-α protein, which have been shown to be strongly associated with HLP. Conclusions This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP, providing evidence at the molecular level for its clinical application in the treatment of HLP.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Zhibitai Capsules are characterized by their ability to regulate blood lipids, prevent cardiovascular diseases, and protect the liver, making them widely used in clinical practice. When combined with low-dose statins for the treatment of coronary artery disease, their lipid-lowering effect is comparable to that of high-dose statins, while exhibiting a lower incidence of adverse reactions. Therefore, this study reviews the drug components, mechanisms of action, clinical applications, adverse reactions, and safety of Zhibitai Capsules, providing theoretical support for their clinical use in lipid regulation.

The use of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and have improved the survival outcomes of advanced patients while offering better overall safety compared to chemotherapy.However, due to immune senescence, the efficacy and safety of immunotherapy in elderly patients are different from those in non-elderly patients.Moreover, most clinical trials have limited data on elderly patients, and immunotherapy in the elderly population lacks high-level evidence-based medical support.This article introduces the theoretical basis of immunotherapy in the elderly population, summarizes clinical data on the efficacy and safety of immunotherapy for advanced NSCLC in the elderly, and analyses the immunotherapy for special subgroups of elderly patients, aiming to provide a reference basis for treating this population.The results showed that single-agent immunotherapy had good efficacy and safety in elderly patients with advanced NSCLC in the age group of 65-74 years, obtaining long-term survival benefits, However, the benefits of immunotherapy in the elderly population ≥75 years old remian unclear, and the outcomes of immunotherapy in the elderly ≥80 years old were poor.In addition, the performance status (PS) score of ≥2 was a significant factor in reducing the efficacy of single-agent immunotherapy in elderly patients.In addition, a pre-treatment PS score of ≥2 was an independent risk factor for reducing the efficacy of immunotherapy alone.Immunotherapy in combination with chemotherapy in the elderly has shown efficacy comparable to the overall population.However, there is an increased incidence of treatment-related adverse events(TRAEs)in patients ≥75 years of age.Dual-immunity combination therapies are not currently recommended for the treatment of advanced NSCLC in the elderly.Elderly patients with brain metastases have poor prognosis, and treatment may consider ICIs in combination with local radiotherapy.Basic research on how to improve the benefit of immunotherapy in elderly patients is also ongoing.In conclusion, the therapeutic prospect of immunotherapy in advanced NSCLC in the elderly is promising, and more exploration is needed in the future.