Lung adenocarcinoma (LUAD) poses a leading cause of cancer-related mortality, necessitating the need for effective and less toxic therapies. Chlorogenic Acid (CGA), a naturally occurring polyphenol, has attracted attention for its potential anti-tumor properties, but its efficacy and mechanisms in LUAD require thorough investigation. To evaluate CGA's potential, we conducted a comprehensive study in a LUAD mouse model. We performed CT scanning and histopathological analysis to confirm its dose-dependent inhibition of tumor growth. Body weight monitoring assessed its lower systemic toxicity compared to cisplatin. Flow cytometry revealed CGA's unique ability to reprogram tumor-associated macrophages by reducing immunosuppressive M2 polarization and promoting anti-tumor M1 phenotypes. Metabolomic profiling identified a significant reduction in the pro-tumor metabolite taurodeoxycholic acid (TDCA) upon CGA treatment. Subsequent in vitro co-culture studies and western blot analysis demonstrated that CGA disrupts the TDCA-activated TGR5/STAT3 signaling axis, which is crucial for M2 macrophage polarization. Our findings unveil a novel immunometabolic mechanism through which CGA suppresses LUAD by remodeling the tumor microenvironment, highlighting its promise as a therapeutic agent or adjunct with both efficacy and a favorable safety profile.

Background:Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their safety profile in patients with thymic epithelial tumors (TETs) remains poorly characterized due to the rarity of these malignancies. Objective:This study aims to comprehensively analyze immune-related adverse events (irAEs) profiles in patients with TETs using real-world pharmacovigilance data. Methods:We conducted a retrospective analysis of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2016 through the fourth quarter of 2024. Cases of TETs with ICI-related adverse events were identified and deduplicated following Food and Drug Administration recommendations. Disproportionality analysis was performed by calculating odds ratios, using the entire US Food and Drug Administration Adverse Event Reporting System database as the reference cohort. Signals were defined as significant with at least 3 cases and a lower 95% CI exceeded 1. Time-to-onset analysis and Weibull Shape Parameter testing were used to characterize the temporal pattern of irAEs. Clinical characteristics between fatal and nonfatal cases and cardiotoxicity specifics were analyzed descriptively. Results:Among 152 eligible TET cases with irAEs, males slightly predominated (80/152, 52.6%), with a median age of 58.5 years. Reports originated predominantly from the United States (51/152, 33.6%) and Japan (16/152, 10.5%). PD-1 inhibitors were implicated in 66.4% (101/152) of cases. Disproportionality analysis identified 14 significant irAE signals across 11 System Organ Classes. Myositis (reporting odds ratio [ROR] 113.15, 95% CI 26.65-480.34), myocarditis (ROR 10.96, 95% CI 5.70-21.07), myasthenia gravis (ROR 3.86, 95% CI 1.86-7.85), and febrile neutropenia (ROR 18.33, 95% CI 4.57-73.55) demonstrated the strongest associations. The median time to irAEs onset was 21.0 days, with 73.2% (41/56) occurring within 2 months of treatment initiation. Fatal outcomes were reported in 23.7% (36/152) of cases and were significantly associated with gender distribution (P=.04) and different treatment strategies (P=.01). The utilization of PD-1 inhibitors was higher in the fatal group (29/36, 80.06%) than in the nonfatal group (72/116, 62.1%). Myocarditis was the most frequent cardiotoxicity, accounting for 51.3% (20/39) of cardiac events. Conclusions:This large-scale pharmacovigilance study delineates a distinct and severe irAEs profile for ICIs in patients with TETs, characterized by robust disproportionality signals for myositis, cardiotoxicity, and myasthenia gravis. As a hypothesis-generating analysis, these findings underscore the need for vigilant monitoring and early detection strategies to mitigate irAE risks, particularly in high-risk subgroups such as patients with thymoma. The results provide clinically relevant evidence to guide risk-benefit evaluation and inform tailored surveillance protocols during ICI therapy in this population.

To develop a predictive model utilizing deep learning by mammography (MG), ultrasound (US), magnetic resonance imaging (MRI), and biopsy whole-slide images (WSI) to evaluate pathological complete response (pCR) of primary lesion after neoadjuvant therapy (NAT) in breast cancer patients. The retrospective investigation was conducted on 397 patients with pathologically proven invasive breast cancer from two Institution. 300 patients from Institution 1 (92 pCR, 208 non-pCR) were randomly divided into training and validation cohorts in a 3:1 ratio. From Institution 2, 97 patients (34 pCR, 63 non-pCR) were included as the independent external test cohort. All patients underwent mammography, ultrasound, and MRI within one month before NAT. ResNet50, DenseNet169, and DenseNet121 convolutional neural networks were employed to develop MG, US, and MRI deep learning model (DLM), respectively. Biopsy slides were collected for evaluation, and the pathology DLM was developed using ResNet34. Clinicopathological data and radiographic characteristics were analyzed by univariate and multivariate logistic regression analysis to determine independent predictors of pCR after NAT, allowing to the establishment of the clinical model. The comprehensive model was assembled by combining MG, US, MRI, pathology, and clinical models. The evaluation of models was conducted by receiver operating characteristic curves, area under the curve (AUC), confusion matrices, accuracy, sensitivity, specificity, and F1 score. Decision curve analysis (DCA) was employed to evaluate the clinical benefits, and the DeLong test was utilized for comparing AUC values between models. Independent predictors of pCR following NAT comprised HER-2 expression status and the minimal ADC value, which were utilized to develop the clinical model. In the training, validation, and external test cohorts, the comprehensive model demonstrated superior performance, with AUCs of 0.870, 0.842, and 0.801, respectively. Compared with the comprehensive model, the DeLong test indicated that the AUC of the clinical model and the mammography model were statistically significant differences (p < 0.05). DCA revealed that the comprehensive model has the highest clinical benefit. The comprehensive model incorporating mammography, ultrasound, MRI, WSI and clinicopathological-radiological features showed certain predictive value for predicting pCR of primary lesion in breast cancer patients following NAT, and the predictive value of the comprehensive model was better than single modality model.

Breast cancer (BC) exhibits significant heterogeneity and complexity and is leading causes of mortality in women globally. Paclitaxel (PTX) is commonly utilized as the primary medication for BC. However, the resistance of BC to PTX poses a significant challenge in clinical treatment. This study aimed at to explore whether carboxy-terminal domain small phosphatase like 2 (CTDSPL2) affected PTX resistance in BC cells. PTX resistant BC cell lines, including MCF-7/PTX and MDA-MB-231/PTX, were developed by continuously increasing PTX concentration, and we found that CTDSPL2 was upregulated in BC cells with PTX resistance. Loss-of-function studies showed that CTDSPL2 knockdown caused a decrease in cytotoxicity and proliferative ability in PTX-resistant BC cells, as well as enhanced cell apoptotic rate and DNA damage. The results from nanoparticle tracking analysis (NTA) indicated that CTDSPL2 knockdown also suppressed the secretion of extracellular vesicles. In vivo tumorigenesis assays showed that CTDSPL2 downregulation inhibited tumorigenicity of nude mice injecting with PTX-resistant BC cells. Co-immunoprecipitation (Co-IP) assay demonstrated the binding between CTDSPL2 and SCY1-like pseudokinase 1 (SCYL1). The increased level of SCYL1 phosphorylation evoked by CTDSPL2 knockdown in PTX-resistant cancer cells was blocked after mutating the serine 754 site of SCYL1 to alanine. In conclusion, the present study identifies CTDSPL2 as a new factor in BC that plays an essential role in PTX-resistant BC cells through the regulation of SCYL1 phosphorylation.

Background:High-risk subsolid pulmonary nodules, especially mixed ground-glass nodules, can represent precancerous or early-stage lung adenocarcinoma spectrum lesions. Standard management relies mainly on risk stratification, repeated thin-slice computed tomography, and invasive diagnosis or surgery when progression suggests malignancy. Safe adjunctive pharmacologic options to reduce nodule progression remain limited. Yifei Sanjie Pill (YFSJ) is an 8-herb traditional Chinese medicine formula that has been previously studied as an adjunctive treatment for non-small cell lung cancer. However, its effect on high-risk pulmonary nodules-a distinct clinical condition-has not yet been investigated. Objective:This protocol describes a multicenter randomized trial evaluating the efficacy, safety, and exploratory mechanisms of YFSJ for preventing high-risk pulmonary nodule progression. Methods:Adults aged 18 to 80 years with single or multiple mixed ground-glass nodules measuring ≤8 mm will be randomized in a 1:1 ratio to receive YFSJ optimized formula granules or matched placebo granules, 2 packets twice daily for 6 months. Both groups will receive guideline-based computed tomography surveillance and any clinically indicated standard diagnostic or therapeutic care. The primary outcome is the 2-year pulmonary nodule progression rate, defined as an increase in the lesion's longest diameter of ≥2 mm, an increase in the solid component of ≥1 mm, or the appearance of a new solid component. Secondary outcomes include lung cancer detection rate, surgery rate, 6-month nodule size and volume change, artificial intelligence-based malignancy risk index, traditional Chinese medicine symptom score, Hospital Anxiety and Depression Scale (HADS) score, Pittsburgh Sleep Quality Index (PSQI) score, safety indicators, and exploratory plasma biomarkers. The primary analysis will use the full analysis set, Kaplan-Meier estimates, log-rank testing, and Cox regression adjusted for center and key covariates; repeated outcomes will be analyzed using mixed-effects models. Results:The study was funded in 2022 and approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (K-2022-131-XZ-01). Recruitment started in June 2023 and was scheduled for completion in December 2025. As of April 2026, a total of 589 participants have completed randomization. The final 2-year follow-up is scheduled for December 2027. Database lock and primary analysis are planned for early 2028, and submission of the first results is expected in spring or summer 2028. Conclusions:This trial will determine whether adding YFSJ to guideline-based surveillance can reduce high-risk pulmonary nodule progression and provide mechanistic evidence for integrative early lung cancer prevention.

Background and Purpose: Squalene epoxidase (SQLE), a key enzyme in cholesterol metabolism, remains underexplored in nasopharyngeal carcinoma (NPC). Additionally, the therapeutic potential of Fangchinoline, an alkaloid with anticancer properties, has yet to be systematically evaluated. This research investigates Fangchinoline's efficacy in NPC treatment and SQLE-related mechanisms. Methods: Drug screening in NPC cell lines C666-1 and 5-8F identified potential candidates. IC50 values were determined using CCK-8 assays, and apoptosis, proliferation, and invasion were assessed via Annexin V/PI staining, EdU staining, and Transwell assays. Cholesterol levels were quantified using a TG kit. RNA sequencing with GO/KEGG analyses identified key pathways. Correlation analysis was performed via cBioPortal and GEPIA2 databases, protein interaction networks via STRING and Cytoscape, and survival analysis via Kaplan-Meier curves. Gene and protein expression were validated with qPCR and Western blot, and an NPC mouse model confirmed in vivo efficacy. Results: Fangchinoline inhibited NPC cell proliferation, induced apoptosis, and reduced cholesterol accumulation. RNA sequencing revealed that Fangchinoline downregulated SQLE expression, suppressing the PI3K/AKT pathway. Correlation and protein interaction analyses highlighted SQLE's role in NPC progression, and survival analysis confirmed its clinical relevance. By targeting SQLE and disrupting cholesterol metabolism, Fangchinoline suppressed tumor growth both in vitro and in vivo. Conclusion: Our study demonstrates that Fangchinoline inhibits NPC growth by targeting SQLE and disrupting the PI3K/AKT pathway, providing new insights into SQLE as a therapeutic target in NPC.

OBJECTIVES:To explore the therapeutic mechanism of Guizhi Fuling (GZFL) Pellets against cervical cancer. METHODS:Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction (PPI) network, followed by GO biological process and KEGG pathway enrichment analysis of the hub genes. The "Traditional Chinese Medicine-Active Ingredients-Targets-Pathways" network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0, and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets. The inhibitory effects of hederagenin, an active ingredient in GZFL Pellets, was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts. RESULTS:GZFL Pellets contain 338 active components targeting 247 action sites. A total of 10127 cervical cancer-related targets were obtained, and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment, including the key targets of GABRA1, PTK2, JAK2, HTR3A, GSR, and IL-17. Molecular docking study showed low binding energies of the active components such as hederagenin, campesterol, and stigmasterol for protein-molecule interaction. GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones, oxidative stress, and lipopolysaccharides. Among the active components of GZFL Pellets, hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells. In nude mice bearing cervical cancer xenografts, hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects. CONCLUSIONS:GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways. Among these components, hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.

EBV infection is closely related to the occurrence and development of gastric cancer (GC). EphA2 is an important oncogenic protein in the progression of a variety of tumors. However, the relationship between EphA2 and EBV in EBV-associated GC (EBVaGC) remains unclear. Immunohistochemical and molecular experiments were performed to compare EphA2 expression between EBVaGC and EBV-negative gastric cancer (EBVnGC). The role of LMP2A in EphA2 expression was evaluated by transfection of LMP2A plasmid or siRNA. The S901 and Y772 phosphorylation site mutant plasmids of EphA2 were constructed to study their biological functions. EphA2 expression was significantly downregulated in EBVaGC tissues and cell lines. LMP2A down-regulates EphA2 expression through the PI3K/AKT signaling pathway and autophagy pathway. pS901-EphA2 and pY772-EphA2 promote the malignant function of GC cells. In addition, pS901-EphA2 promotes the lytic reactivation of EBV by activating the JNK signaling pathway. Our data suggests that pS901-EphA2 and pY772-EphA2 play a role in the malignant characteristics of GC, and that pS901-EphA2 induced phosphorylation of JNK is a potential mechanism by which EphA2 promotes the lytic reactivation of EBV. LMP2A is involved in EBVaGC progression and maintenance of EBV latent infection by down-regulating EphA2 expression.

To investigate the impact of varying levels of chronic stress on the disease-free survival (DFS) and overall survival (OS) of patients with hepatocellular carcinoma (HCC) following curative treatment and establish a comprehensive evaluation index for chronic stress. Ninety HCC patients who underwent curative treatment were assessed for chronic stress using hair cortisol concentration, Stress Score, and the Perceived Stress Scale (PSS-10). The optimal cut-off values for these markers were statistically determined, and correlations among them were analyzed to create the Chronic Stress Index (CSI), which classified patients into high or low chronic stress groups. DFS and OS were compared between the groups. Additionally, a systematic review of literatures on the effects of chronic stress and cancer recurrence was conducted. The optimal cut–off values of the Stress Score, PSS-10, and hair cortisol concentration were 15.30, 50.00 and 19.70 pg/mg, respectively. Patients with a CSI score of 3 to 4 were classified into the low chronic stress state (LCSS) group, whereas those scoring 5 to 6 were classified into the high chronic stress state (HCSS) group. Patients in the HCSS group had significantly reduced DFS (P < 0.001) and OS (P = 0.033) compared to the LCSS group. The systematic review identified only three clinical trials on chronic stress and cancer recurrence. High chronic stress levels are associated with shorter DFS and OS in HCC patients. The CSI classification effectively categorized the chronic stress state, providing a novel tool for clinical evaluation.

Nano-assembly particles (NAPs) isolated from Traditional Chinese Medicine (TCM) formulations retain a better multi-component overall effect than isolated single active ingredient, which gradually emerging as a transformative approach for the pharmacodynamic and pharmacological research of TCM. This study introduced an innovative research paradigm for investigating the mechanisms of TCM formulas and proposes the groundbreaking concept of “TCM nano-formulated prescriptions” using Yi-Fei-San-Jie Formula (YFSJF) as a clinically study model. Firstly, based on the favorable outcomes in 31 clinical patients with pulmonary space-occupying lesions who received YFSJF treatment, the anti-tumor efficacy of NAPs isolated from the YFSJF decoction was systematically evaluated. Furthermore, the basic material components and underlying mechanism of NAPs were elucidated. Finally, 248 artificially synthetic nanoparticles developed by central bioactive components of YFSJF were used to study the self-assembly process, anti-tumor activity and safety profile. This study firstly demonstrated the potential NAPs-based replacement of traditional formulas and establishes a pioneering methodology for screening multi-component NAPs.

Background/Objectives: Finotonlimab (SCTI10A) is a humanized anti-PD-1 antibody tested in Phase III trials for several solid tumor types. Methods: This study characterized the in vitro and in vivo efficacy, Fc-mediated effector function, and non-clinical PK/PD properties of finotonlimab. Results: The results demonstrated that finotonlimab is effective in stimulating human T cell function in vitro and exhibits marked antitumor efficacy in vivo using both PD-1-humanized and PBMC-reconstructed mouse models. Additionally, finotonlimab exhibited minimal impact on the activation of effector cells via Fc receptor-dependent pathways, potentially facilitating PD-1+ T cell killing. In cynomolgus monkeys, finotonlimab exhibited a nonlinear pharmacokinetic (PK) profile in a dose-dependent manner, and a receptor occupancy rate of approximately 90% was observed at 168 h following a single administration of 1 mg/kg. Finotonlimab’s PK profile (especially Cmax) was better than that of marketed antibodies. Following a 13-week successive administration of finotonlimab, a pharmacodynamic analysis revealed that a sustained mean receptor occupancy of PD-1 molecules on circulating T cells remained at or above 93% for up to 8 weeks, even at a dose of 3 mg/kg, and that there were higher antibody accumulations in different dose groups. Conclusions: Taken together, the preclinical findings are promising and provide the groundwork for evaluating the efficacy and pharmacodynamic characteristics of finotonlimab in clinical trials.

While cancer-associated fibroblasts (CAFs) significantly influence tumor progression, their temporal dynamics remain poorly understood. We investigated time-dependent interactions between non-small cell lung cancer (NSCLC) cells and CAFs, and evaluated rosmarinic acid (RA)'s potential to modulate these interactions. HCC827 lung adenocarcinoma cells and MRC-5 fibroblasts were co-cultured in vitro. CAF activation markers (α-SMA, FAP) and epithelial-mesenchymal transition (EMT) were assessed through morphological and molecular analyses. Xenograft models with different tumor-to-fibroblast ratios (1:1, 1:2) evaluated tumor growth dynamics and RA's therapeutic effects combined with gefitinib. Time-course analysis revealed a biphasic pattern in tumor-CAF interactions. CAF activation markers reached peak levels by day 6, followed by maximal EMT marker expression in NSCLC cells at day 8. In xenograft models, higher CAF proportions initially inhibited tumor growth but accelerated tumor progression. RA treatment significantly attenuated CAF activation markers and reversed EMT-related changes in cancer cells, leading to reduced tumor growth in CAF-enriched xenografts. The combination of RA with gefitinib demonstrated enhanced anti-tumor effects compared to gefitinib alone. CAFs exhibit temporally biphasic roles in NSCLC progression characterized by initial suppression followed by promotion of tumor microenvironment deterioration. RA effectively modulates these tumor-stromal interactions, enhances gefitinib efficacy, and delays the development of drug resistance.

Background: Non–small‐cell lung cancer remains the leading cause of cancer‐related deaths globally, and epidermal growth factor receptor mutations have been identified as crucial drivers of the disease. Encouragingly, epidermal growth factor receptor tyrosine kinase inhibitors have demonstrated promising clinical outcomes. Nonetheless, the emergence of resistance to third‐generation EGFR‐TKIs like osimertinib and almonertinib is an inevitable challenge. Methods: In this study, we generated almonertinib‐resistant cell lines from H‐1975 and HCC827 lung cancer cell lines. We utilized various assays, including cell proliferation assays, hematoxylin and eosin staining, and cell cycle assays, to investigate the characteristics of drug‐resistant cells. Additionally, we performed RNA transcriptome sequencing to identify differentially expressed genes (DEGs) in almonertinib‐resistant cells. To further expand our analysis, we obtained sequencing data of osimertinib‐resistant cells from the Gene Expression Omnibus (GEO) dataset and identified DEGs in these cells. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to assess the biological functions and signaling mechanisms associated with DEGs. Furthermore, the survival prognosis and immune cell infiltration of common differentially expressed genes (co‐DEGs) in osimertinib—and almonertinib‐resistant cells were analyzed, and the expression of a co‐DEG ( IGFBP7 ) was verified through quantitative reverse transcriptase polymerase chain reaction (qPCR) and western blotting (WB) assays. Gene knockdown plasmids were constructed for cell transfection, and the invasive ability of resistant cells was assessed using a Transwell assay following the knockdown of IGFBP7 . Results: Experimental cell counting kit–8 cytotoxicity studies revealed intriguing findings regarding drug resistance in lung cancer cells. Specifically, the IC 50 values and resistance factors of H‐1975 and HCC827 cells were found to be 1.9 nM and 833.58 and 2.2 nM and 631.95, respectively. In addition to these quantitative results, comparative observations of the cell morphology and cell cycle revealed significant alterations in drug‐resistant cells. Transcriptome sequencing analysis identified 220 DEGs between H‐1975 and H‐1975/AR and 736 DEGs between HCC827 and HCC827/AR. Interestingly, screening of overlapping DEGs with osimertinib‐resistant cells in the GEO database identified some common genes, such as IGFBP7 and RFTN1 , which were found to be associated with the improved prognosis of non–small–cell lung cancer by survival analysis. Furthermore, GO analysis and KEGG pathway enrichment analysis revealed different pathway changes in different drug‐resistant cells. Survival analysis indicated that a higher expression of co‐DEGs ( IGFBP7 , RFTN1 ) was associated with a more favorable prognosis. Furthermore, IGFBP7 expression is strongly associated with infiltration levels of CD8+ T cells, Tregs, and macrophage cells in lung adenocarcinoma. Molecular biology experiments confirmed that the mRNA and protein expression level of IGFBP7 were over‐expressed in almonertinib‐resistance cells. H‐1975/AR cells were transfected with si‐ IGFBP7 , and the results of transfection were verified at the mRNA and protein levels. After knocking down gene expression, the IC 50 of the cells was 0.3 ± 0.02 µM, which was significantly lower than that of untransfected cells. Additionally, the invasion of cells in the knockdown group was repressed. Conclusions: These findings indicated that almonertinib and osimertinib exhibited distinct resistance mechanisms in vitro, underscoring the need for tailored treatment approaches.

Iron is crucial for cell survival and maintaining normal physiological functions. Viral infections can disrupt cellular iron metabolism, leading to inflammation and cancer. Ferritin, a key iron-binding protein, consists of ferritin heavy chain 1 (FTH1) and ferritin light chain (FTL) and helps regulate systemic iron balance, both implicated in various tumor developments. Epstein-Barr virus (EBV), the first oncogenic virus discovered in humans, can induce the development of EBV-associated gastric cancer (EBVaGC). However, the regulatory mechanisms and functions of FTH1 and FTL in EBVaGC are poorly understood. This study aimed to investigate how EBV regulates FTH1 and FTL and their roles in the development of EBVaGC. We show that EBV is able to remodel intracellular iron metabolism, affecting the expression of FTH1 and FTL. EBV-encoded LMP2A promotes the expression of FTH1 and FTL by up-regulating p62 and blocking the autophagy degradation pathway, thus participating in the occurrence and development of EBVaGC. Knocking down FTL inhibits cell migration and proliferation, and promotes apoptosis, whereas FTH1 knockdown has negligible effects on these cellular functions. Additionally, we found that ferritin enhanced the inflammatory state of gastric cancer cells. Overall, our findings highlight the significant impact of EBV on ferritin, underscoring a previously unrecognized role of ferritin in the progression of EBVaGC. This novel pathway could offer new therapeutic targets for the treatment of EBVaGC.

Evidence regarding Chinese herbal medicine for facial rash related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is limited. Therefore, this study aimed to investigate whether ex ternal application of a Xiaozhen zhiyang (XZZY) decoction is effective for EGFR-TKI-related facial rash in Chinese patients. In this prospective cohort study, 123 participants with EGFR-TKI-related facial rash were recruited from July 18, 2019 to May 20, 2021. The intervention was external application of the XZZY decoction twice daily for 2 weeks using a facial mask. Treatment efficacy, change in the WoMo score, and quality of life were evaluated as endpoints. The average age of the 123 enrolled participants was 54.83 ± 12.45 years, and 48.78% were female. The total efficiency of treatment was 93.5%, including 12 (10%) cases were cured, 20 (16.26%) cases were markedly improved and 83 (67.48%) cases were improved. The generalized estimating equations showed decreased WoMo scores, itching, and pain, as well as an improved quality of life after the treatment. Only 1 participant reported skin allergies, and no other adverse effects were reported. This study showed the effectiveness and safety of a XZZY decoction for EGFR-TKI-related rash.

ETHNOPHARMACOLOGICAL RELEVANCE:Lichong Decoction (LCD), a classical herbal formula, has been widely applied in clinical practice. Studies have validated its effectiveness in combating cancer; nevertheless, the exact pathways through which it influences colorectal cancer require further investigation. AIM OF THE STUDY:The mechanism of LCD in inhibiting colorectal cancer progression was investigated. MATERIALS AND METHODS:BALB/c-nu mice were xenografted with colorectal cancer cells to establish an animal model. The chemical constituents of LCD were characterised using high-performance liquid chromatography. Quantitative real-time PCR was employed to assess the expression levels of Rab27B mRNA. The Cancer Genome Atlas data of patients with colorectal cancer were used for gene clinical correlation analysis. Lentiviral transfection was used to construct stable cell lines. Cell motility was analysed using wound-healing and invasion assays. Pathological changes were observed using haematoxylin and eosin staining. Protein expression was determined using immunohistochemistry and western blotting. The results were statistically analysed using GraphPad Prism 10.1. 2. RESULTS:In vivo, LCD treatment led to a substantial decrease in the size of colorectal cancer tumours. Importantly, LCD markedly lowered the expression of Rab27B and proteins related to the PINK1/Parkin pathway in tumour tissues. In vitro, LCD significantly reduced the expression of Rab27B in colorectal cancer cells. Consistent with the results in vivo, the reduction in Rab27B inhibited PINK1/Parkin signalling protein expression and prevented the migration and invasion of colorectal cancer cells. CONCLUSIONS:Lichong Decoction inhibits colorectal cancer growth by dampening PINK1/Parkin signalling in colorectal cancer cells through repressing Rab27B.

Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and the immunosuppressive nature of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components of the TME. M2-like TAMs are essential in facilitating tumor metastasis as well as augmenting the drug resistance of tumors. This review encapsulates the mechanisms that M2-like TAMs use to promote tumor drug resistance. We also describe the emerging therapeutic strategies that are currently targeting M2-like TAMs in combination with other antitumor drugs, with some still undergoing clinical trial evaluation. Furthermore, we summarize and analyze various existing approaches for developing novel drugs that target M2-like TAMs to overcome tumor resistance, highlighting how targeting M2-like TAMs can effectively stop tumor growth, metastasis, and overcome tumor drug resistance.

BackgroundThis study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC).MethodsWe used differentially expressed analysis and weighted gene co-expression network analysis (WGCNA) to identify key genes and modules in HGNEC. KEGG and GO analyses helped understand these genes’ roles, and ROC curves assessed their diagnostic value. We also studied SNAP25’s relation to immune infiltration and confirmed findings with in vitro and vivo experiments and datasets.ResultsWGCNA identified 595 key genes related to pathways like MAPK signaling, GABAergic synapse, and cancer-related transcriptional misregulation. Top genes included SNAP25, MYC, NRXN1, GAD2, and SYT1. SNAP25 was notably associated with M2 macrophage infiltration. Dataset GSE40275 confirmed SNAP25’s high expression and poor prognosis in HGNEC. qRT-PCR and WB analyses showed increased SNAP25 and c-MYC levels in HGNEC, promoting MEK/ERK pathway activity. Reducing SNAP25 decreased H1299 cell proliferation, migration, invasion, and levels of c-MYC, MEK, and ERK. Finally, in vivo experiments further confirmed that SNAP25 knockout can inhibit tumor growth.ConclusionSNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.

BACKGROUND Neoadjuvant immunochemotherapy (nICT) has emerged as a popular treatment approach for advanced gastric cancer (AGC) in clinical practice worldwide. However, the response of AGC patients to nICT displays significant heterogeneity, and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes. AIM To establish a radiomic model to predict the response of AGC patients to nICT. METHODS Patients with AGC who received nICT (n = 60) were randomly assigned to a training cohort (n = 42) or a test cohort (n = 18). Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT. An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature. The performance of all the models was assessed through receiver operating characteristic curve analysis, decision curve analysis (DCA) and the Hosmer-Lemeshow goodness-of-fit test. RESULTS The radiomic nomogram could accurately predict the response of AGC patients to nICT. In the test cohort, the area under curve was 0.893, with a 95% confidence interval of 0.803-0.991. DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models. CONCLUSION A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC. This tool can assist clinicians in treatment-related decision-making.

RATIONALE AND OBJECTIVE:To investigate the MR characteristics of phlegmonous stage and abscess stage primary spinal epidural abscess. MATERIALS AND METHODS:This study retrospectively analyzed the clinical and imaging characteristics of 27 cases of pathologically confirmed primary spinal epidural abscess. Predisposing conditions of all patients were collected. All patients underwent conventional magnetic resonance imaging, while fifteen patients also underwent post-contrast magnetic resonance imaging. RESULTS:The initial symptoms included back pain in 25 patients, fever in 18, motor deficit in five, and sensory changes in 13. Underlying diseases included distant site of infection in seven, injection therapy in five, neoplasm in five, chronic inflammatory disease in five, diabetes mellitus in four, alcoholism in three, metabolic disorder in three, hepatopathy in three, and obesity in two. Abscess location was ventral epidural space in 15 patients (55.6%) and dorsal epidural space in 12 (44.4%). On T1-weighted image, the abscess was hypointense to the spinal cord in 23 patients (85%) and isointense in four (15%). All abscesses were hyperintense to the spinal cord on T2-weighted image. Among the 15 patients who underwent contrast-enhanced imaging, ring enhancement was present in 13 and homogeneous enhancement in two. Adjacent vertebrae body edema was present in four patients. The abscess was purely intraspinal in 25 patients (92.6%). Paraspinal extension was present in two (7.4%). CONCLUSION:Primary spinal epidural abscess patients have one or more predisposing conditions. Phlegmonous stage primary spinal epidural abscess appears isointense on T1WI and hyperintense on T2WI and enhancement is homogeneous. Abscess stage primary spinal epidural abscess hyperintense on T2WI and hypointense on T1WI and ring enhancement. Presence of vertebral body edema is an important sign to help diagnose primary spinal epidural abscess.