OBJECTIVE To systematically evaluate the correlation between dynamic changes in inflammatory markers during treatment with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in non-small cell lung cancer （NSCLC） patients and therapeutic efficacy， with the aim of providing evidence-based support for clinical prognosis assessment and treatment strategy adjustment. METHODS Databases including PubMed， Embase， Cochrane Library， CNKI， Wanfang Data， and CBM were searched from the inception to July 20， 2025. Following literature screening， data extraction and quality assessment， descriptive analysis was conducted on the outcomes of included studies. RESULTS A total of eight studies were included to analyze the correlation of 6 inflammatory markers before and after treatment with EGFR-TKIs with therapeutic efficacy. The risk of bias assessment identified six high-quality studies and two moderate-quality studies. Among these studies， seven studies demonstrated that lower levels of neutrophil-to-lymphocyte ratio （NLR）， derived neutrophil-to-lymphocyte ratio （dNLR）， platelet-to-lymphocyte ratio （PLR）， and monocyte-to-lymphocyte ratio （MLR）， higher lymphocyte-to-monocyte ratio （LMR） before treatment， as well as decreased NLR and MLR and increased LMR after treatment were associated with longer median progression-free survival. Five studies indicated that lower levels of NLR， dNLR， PLR， and interleukin-6 （IL-6）， higher LMR before treatment as well as decreased NLR and dNLR and increased LMR were associated with longer median overall survival. Three studies indicated that lower levels of IL-6 were associated with a higher objective response rate， while the association of these markers after treatment remained controversial； another study showed that an early decline in NLR， MLR， and PLR after treatment may be associated with objective response benefit. CONCLUSIONS Lower inflammatory levels during EGFR-TKIs therapy correlate with better therapeutic efficacy in NSCLC patients.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

The aim of this research was to investigate the mechanism of chelidonine on H2 O2-in-duced inflammatory injury in porcine intestinal epithelial cells(IPEC-J2)through transcriptome sequencing.IPEC-J2 cells in the logarithmic growth phase were divided into the blank group(K group),H2O2 group(S group)and chelidonine group(L group),with three replicates in each group.Total RNA was isolated from each group for the purpose of constructing a sequencing li-brary.The assembled data underwent functional annotation,differential gene analysis,as well as GO and KEGG enrichment analyses.qPCR was used to confirm the expression of key differentially expressed genes(DEGs),and ELISA was utilized to assess the effect of chelidonine on the permea-bility of IPEC-J2 cells.The results indicated that the sequencing data met the necessary criteria and demonstrated a strong correlation between samples.The GO functional annotation results suggest that the intervention effects of chelidonine involve biological processes such as oxidative stress re-sponse and G2/M phase transition regulation of the mitotic cycle,and are closely associated with molecular functions,such as transmembrane transport activity.The KEGG enrichment analysis indicates that following H2 O2 treatment,DEGs in IPEC-J2 cells are predominantly enriched in the p53 signaling pathway,the coagulation cascade,the FoxO signaling pathway,and various other sig-naling pathways.Following pretreatment with chelidonine,the DEGs exhibit significant enrichment in several signaling pathways related to inflammation,including the TNF signaling pathway,syn-aptic vesicle cycle,and IL-17 signaling pathway.The results of qPCR were consistent with the se-quencing results.Chelidonine has also been found to effectively inhibit LDH release,elevate GLN content,and decrease DOA content.In conclusion,it can be seen that chelidonine can reduce cell permeability and alleviate H2 O2-induced inflammatory injury in IPEC-J2 cells by modulating in-flammation-related pathways such as the TNF signaling pathway.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely present in the environment. They can enter the human body through multiple pathways such as air, water, and diet, and tend to bioaccumulate. In recent years, increasing attention has been paid to the potential impacts of PFAS exposure on male reproductive health. This review systematically summarizes the characteristics of PFAS exposure in men and its effects on semen quality. Epidemiological evidence indicates that PFAS exposure is significantly associated with reduced sperm concentration, motility, and normal morphologyrate. Mechanistic studies suggest that PFAS may induce male reproductive toxicity through various pathways, including germ cell cytotoxicity, dysfunction of Sertoli cells, endocrine disruption, oxidative stress, and epigenetic regulation. This review aims to integrate current evidence to support the assessment of male reproductive risks associated with PFAS exposure and to inform the development of preventive strategies.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely present in the environment. They can enter the human body through multiple pathways such as air, water, and diet, and tend to bioaccumulate. In recent years, increasing attention has been paid to the potential impacts of PFAS exposure on male reproductive health. This review systematically summarizes the characteristics of PFAS exposure in men and its effects on semen quality. Epidemiological evidence indicates that PFAS exposure is significantly associated with reduced sperm concentration, motility, and normal morphologyrate. Mechanistic studies suggest that PFAS may induce male reproductive toxicity through various pathways, including germ cell cytotoxicity, dysfunction of Sertoli cells, endocrine disruption, oxidative stress, and epigenetic regulation. This review aims to integrate current evidence to support the assessment of male reproductive risks associated with PFAS exposure and to inform the development of preventive strategies.