Colorectal cancer is one of the malignant tumors with high incidence and mortality rates worldwide. Its diagnostic and therapeutic strategies are continuously updated with the development of molecular biology and precision medicine. Based on the important updates from three international authoritative guidelines in 2024: the European Society for Medical Oncology (ESMO), the National Comprehensive Cancer Network (NCCN), and the Chinese Society of Clinical Oncology (CSCO), this article systematically compares and interprets the latest advancements of colorectal cancer in molecular detection, targeted therapy, immunotherapy, chemotherapy and local therapy. Through an in-depth comparison and analysis of the three guidelines, this article aims to provide clinicians with the latest diagnostic and therapeutic references, and to promote the standardization and precision of colorectal cancer treatment in China.

Src, which is a non-receptor tyrosine kinases (NRTKs), is a member of the Src-family of protein kinases (SFKs). Studies have shown that high expression of Src protein kinase in tumor patients is associated with poor prognosis and reduced survival. This suggests that inhibiting Src expression may be a promising therapeutic strategy for cancer treatment. Currently, several Src inhibitors have been approved for clinical use in the treatment of malignant tumors, and studies on the delivery of Src inhibitors using nanotechnology have also achieved certain progress in basic research. This review summarizes the latest research progress on the delivery of Src inhibitors using nanoparticles, aiming to provide a theoretical basis for the development and application of novel cancer therapeutics based on nanomaterial carriers.

Objectives: Patients with brain metastasis of renal cancer have poor prognosis and are mostly excluded from clinical drug studies. With the improvement of survival brought by local control, some patients can further receive active targeted and immune drug therapy. This study retrospectively analyzed the clinical characteristics and treatment of patients with brain metastasis of renal cancer, aiming to provide references for the selection of clinical treatment programs.

Methods: Clinical data of 39 patients with renal cancer with brain metastasis diagnosed and treated in the Department of Oncology at Huashan Hospital, Fudan University, from February 2018 to October 2023 were retrospectively analyzed. Kaplan-Meier method was used to estimate survival, and Log-rank test was used to compare the differences in survival. COX regression model was used to analyze the effects of gender, age, Performance Status score, time of occurrence of brain metastasis, number of brain metastases, location of brain metastases, neurological symptoms, extracranial metastases, surgery, radiotherapy, targeting and immunotherapy on patient survival.

Results: Of the 39 patients with renal cancer with brain metastasis the median survival after brain metastasis was 34 months [95% confidence interval (CI): 19.4-48.6]. Univariate analysis showed that patients with multiple brain metastases (P＝0.009) and patients with less than 1 year from the diagnosis of renal cancer to the occurrence of brain metastasis (P＝0.003) had worse prognosis. Multivariate analysis suggested that multiple brain metastases and the time from diagnosis of renal cancer to brain metastasis ≤1 year were independent risk factors for survival. There was no significant difference in overall survival between systemic treatment after brain metastasis surgery and systemic treatment after brain metastasis radiotherapy (22 months vs 24 months, P＝0.908). Overall median survival was 48 months (95% CI: 28.6-67.4) in patients with single brain metastasis who received local treatment (26 cases), and there was no difference in total over survival time among those who received further systemic treatment after local treatment.

Conclusion: For brain metastasis of renal cancer, patients with multiple brain metastases and patients whose time from diagnosis of renal cancer to occurrence of brain metastasis was less than 1 year had worse prognosis. The survival benefit of systemic therapy after brain metastasis surgery was comparable to that of systemic therapy after brain metastasis radiotherapy. Some patients with single brain metastasis can have a longer survival after local treatment, and whether they receive further systemic treatment does not affect overall survival. However, the optimal treatment plan still requires further exploration through prospective studies.

Soft tissue sarcoma (STS) is a rare malignant tumor originating from mesenchymal tissues, with over 50 histological subtypes and significant clinical heterogeneity, making treatment particularly challenging. Although comprehensive treatment primarily focusing on surgical resection plays an important role in local control, the prognosis for patients with advanced or metastatic disease remains poor, and the benefits of traditional chemotherapy are limited. In recent years, with advances in molecular biology and genomics, targeted therapy has emerged as a new treatment strategy for STS, enabling effective modulation of tumor biological behavior through precise identification of driver genes and abnormal signaling pathways. Currently, anti-angiogenic agents, multi-target tyrosine kinase inhibitors (TKIs), mammalian target of rapamycin (mTOR) and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, as well as novel agents targeting neurotrophic tyrosine receptor kinase (NTRK) fusions and enhancer of zeste homolog 2 (EZH2) epigenetic regulation, have all demonstrated clinical benefits in various STS subtypes. This review summarizes recent progress in molecular targeted therapy for STS, including combination treatment strategies and resistance mechanisms, and discusses its clinical application prospects and existing challenges, aiming to provide a reference for clinical practice. In the future, continuous exploration of new molecular targets, optimization of combination regimens, and overcoming drug resistance will be essential to advance STS treatment towards precision and personalization, ultimately bringing longer survival and improved quality of life for patients.

Lung cancer is the deadliest malignancies worldwide. Among its subtypes, non-small cell lung cancer (NSCLC) is the most common pathological phenotype, and its treatment primarily relies on surgery, chemoradiotherapy, targeted therapy, and immunotherapy. In recent years, immunotherapy has shown unique advantages in controlling NSCLC progression, but its efficacy is heavily restricted by T-cell exhaustion within the tumor microenvironment. The T-cell exhaustion involves multidimensional mechanisms including continuous antigen stimulation, imbalanced cytokines, transcriptional regulation abnormalities, epigenetic modifications, and chromosomal structural remodeling, which has become a focal point in tumor immunology research. Studies targeting T-cell exhaustion mechanisms are considered to hold potential for overcoming current immunotherapy limitations. This review systematically summarizes the recent clinical and fundamental research advances on T-cell exhaustion in NSCLC, aiming to provide insights for further understanding the immune evasion mechanisms of NSCLC and to inform the development of novel immunotherapy strategies.

Objective: Retroperitoneal liposarcoma is a rare malignant tumor derived from fat cells, and its clinicopathological characteristics remain unclear. This study aims to explore the clinicopathological characteristics of retroperitoneal liposarcoma in the Chinese population based on nearly 20 years of diagnosis and treatment experience in a single center.

Methods: We retrospectively collected the clinical and pathological data of patients with retroperitoneal liposarcoma who were diagnosed and treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from 2004 to 2023. Recurrence and prognosis information of the patients was obtained through outpatient follow-up or telephone follow-up.

Results: Over the past 20 years, Renji Hospital has diagnosed and treated a total of 172 patients with retroperitoneal liposarcoma, including 96 males and 76 females. These patients have undergone 297 hospitalizations and 228 surgeries at Renji Hospital. The overall survival rates at 3, 5, and 10 years were 73.3%, 60.0%, and 36.8%, respectively. The pathological subtype transformation rate of retroperitoneal liposarcoma was 32.2%. On average, each patient underwent 2.3 surgeries, with the maximum number of surgeries being 12. In addition to the tumor, 52.8% of patients had surrounding organs resected, with the kidney (21.0%) being the most commonly resected organ. The perioperative mortality rate was 2.2%, and the incidence of unplanned reoperations was 1.8%. The overall complication rate was 15.4%, with small bowel obstruction being the most common complication (21.2%). 13.1% of patients received adjuvant therapy other than surgery. However, only one patient received systematic adjuvant therapy according to the guidelines at that time.

Conclusion: Retroperitoneal liposarcoma is a rare malignant disease with favorable prognosis. Surgery is the main method to treat retroperitoneal liposarcoma, and postoperative recurrence is the biggest obstacle to its therapeutic effect. Currently, standardized adjuvant therapy for retroperitoneal liposarcoma still needs to be strengthened, and the development of effective drugs is also a direction that requires significant attention in the future.

Retroperitoneal liposarcoma poses significant therapeutic challenges due to its unique anatomical location and biological characteristics. Recent advancements in surgical techniques, the optimization of radiotherapy strategies, and the development of novel pharmacological agents have greatly transformed the treatment landscape. Surgical management has shifted from solely focusing on radical resection to strategies that balance complete tumor removal and organ function preservation. Multidisciplinary team approaches have demonstrated significant improvements in patient prognosis by integrating expertise across surgery, radiology, pathology, and oncology. Radiotherapy, supported by precision techniques, serves as a complementary treatment for local tumor control. However, its efficacy remains constrained by factors such as tumor histology and radiation dosage limitations. In pharmacotherapy, traditional cytotoxic chemotherapy is increasingly being supplanted by targeted therapies and immunotherapy combinations, while breakthroughs in molecular subtyping and liquid biopsies are paving the way for personalized treatment approaches. Looking ahead, the integration of radiomics, artificial intelligence-supported treatment strategies, and multimodal combination therapies is expected to advance retroperitoneal liposarcoma management. This evolution is anticipated to achieve a better balance between radical surgical intervention and quality-of-life preservation, thus delivering substantial survival benefits and improved outcomes for patients.

Objectives: To investigate the relationship between postoperative frailty and nutritional status in elderly patients with gastrointestinal tumors.

Methods: Elderly patients with gastrointestinal tumors who underwent elective surgery at Renji Hospital, Shanghai Jiao Tong University School of Medicine from December 2022 to April 2023 were enrolled as the study objects. Clinical Frailty Scale (CFS) was used to assess postoperative frailty, and geriatric nutritional risk index (GNRI) was used to assess preoperative and postoperative nutritional risk. Demographic data and nutrition-related laboratory indicators were collected to analyze the risk factors for postoperative frailty in elderly patients with gastrointestinal tumors.

Results: A total of 242 patients were included, among whom 54 (22.31%) developed postoperative frailty. Multivariate binary logistic regression analysis showed that advanced age, higher preoperative serum albumin level, lower preoperative GNRI and postoperative serum albumin level were independent risk factors for postoperative frailty in elderly patients with gastrointestinal tumors (P<0.05). The receiver operating characteristic (ROC) curve analysis demonstrated that preoperative serum albumin level, preoperative GNRI, and postoperative serum albumin level all had certain predictive value for postoperative frailty. Their areas under the curve (AUC) were 0.652 [95% confidence interval (CI): 0.565-0.738], 0.724 (95% CI: 0.645-0.803) and 0.914 (95% CI: 0.873-0.955), respectively. Postoperative serum albumin level showed the best predictive performance, with an accuracy rate as high as 91.4%.

Conclusion: In this study, the incidence of postoperative frailty in elderly patients with gastrointestinal tumors was 22.31%. Age, preoperative serum albumin level, preoperative GNRI and postoperative serum albumin level were independent factors of postoperative frailty in elderly patients with gastrointestinal tumors. Among these, postoperative serum albumin level was the best predictor of postoperative frailty in elderly patients with gastrointestinal tumors.

Objective: To construct a nano delivery system based on sonodynamic therapy to overcome cisplatin resistance of ovarian cancer by inducing pyroptosis.

Methods: A human cisplatin-resistant ovarian cancer cell line (SKOV-3/DDP) was successfully induced using a stepwise concentration gradient induction method. A composite nanoparticles (BTO/ZIF) with a core of barium titanate (BaTiO₃, BTO) and a shell of zeolitic imidazolate framework-8 (ZIF-8) was constructed. The surface of BTO/ZIF was further coated with DSPE-PEG₁₀₀₀-Pt (Ⅳ) and DSPE-PEG₁₀₀₀-AF to prepare the targeted nanoparticle BTO/ZIF@AF/Pt. The morphology, size, structure, hydrodynamic diameter, and colloidal stability (Zeta potential) of BTO/ZIF@AF/Pt nanoparticles were characterized using transmission electron microscopy, scanning electron microscopy, and Malvern particle size analyzer. The reactive oxygen species (ROS) generation capability of BTO/ZIF composite nanoparticles was assessed by ultraviolet-visible (UV) spectrophotometry and DCFH-DA probe assay. Cellular uptake of BTO/ZIF@AF/Pt nanoparticles by SKOV-3/DDP cells was verified using confocal laser scanning microscopy. Under ultrasound irradiation, the effects of BTO/ZIF@AF/Pt nanoparticles on the expression of pyroptosis-related proteins and sensitivity to cisplatin chemotherapy were examined by Western blotting.

Results: In this study, a human cisplatin-resistant ovarian cancer cell line (SKOV-3/DDP) was successfully induced, and a targeted delivery nanoparticle using BTO and metal-organic framework (MOF) composite materials as the carrier for cisplatin was also successfully constructed. Under ultrasound stimulation, BTO/ZIF@AF/Pt nanoparticles effectively generated ROS and induced pyroptosis in ovarian cancer SKOV-3/DDP cells.

Conclusion: Ultrasound-triggered ROS generation from BTO/ZIF@AF/Pt nanoparticles, combined with Zn^2＋ release, synergistically promotes ROS-induced pyroptosis in ovarian cancer SKOV-3/DDP cells, thereby effectively overcoming cisplatin resistance.

Retroperitoneal sarcoma (RPS) is a kind of highly heterogeneous soft tissue tumor. Radical surgery remains the mainstay of treatment. However, the high postoperative local recurrence rate significantly impacts long-term survival. The efficacy of traditional systemic chemotherapy in RPS is limited, necessitating the exploration of more effective adjuvant treatment strategies to reduce the local recurrence rate. This paper summarizes the current status of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of RPS, along with recent advances in basic and clinical research. We explore the potential value of HIPEC in reducing postoperative recurrence of soft tissue sarcomas and improving patient prognosis. The combination of cytoreductive surgery (CRS) and HIPEC has been shown to prolong both disease-free survival and overall survival in RPS patients, with particular benefits observed in specific pathological subtypes such as leiomyosarcoma and dedifferentiated liposarcoma. However, large-scale prospective studies on the efficacy of HIPEC in preventing postoperative recurrence of RPS are still lacking. Future research should focus on conducting multi-center, large-scale prospective studies to further validate the efficacy of HIPEC in RPS and to define the patient populations that may benefit the most from this approach.

Objective: To investigate whether aurora kinase A (AURKA) in hepatocellular carcinoma (HCC) cells drives M2 polarization of macrophages via exosomes, and to clarify its underlying molecular mechanism.

Methods: The correlations between AURKA expression level in HCC tissues and M2 macrophage infiltration as well as prognosis of HCC patients were analyzed using the GEPIA (Gene Expression Profiling Interactive Analysis) and TIMER (Tumor Immune Estimation Resource) public databases. Based on the human HCC cell line MHCC-97H, AURKA stably overexpressed (97H-AKAOE) and knockdown (97H-AKAKD) cells were constructed. Exosomes were isolated by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Exosomes derived from 97H-AKAOE and 97H-AKAKD cells were co-cultured with M0 macrophages, and the expression levels of M2 macrophage marker proteins CD163 and Arg-1 were assessed by real-time quantitative reverse transcription PCR (RT-qPCR) and Western blotting to evaluate the effect of AURKA on M2 polarization of macrophages. Liquid chromatography-mass spectrometry (LC-MS) was used to identify key differentially expressed proteins regulated by AURKA in exosomes, and functional rescue experiments were performed to validate their roles on M2 polarization of macrophages.

Results: AURKA was highly expressed in HCC tissues, and its expression level positively correlated with poor prognosis of HCC patients and M2 macrophage infiltration abundance (all P < 0.05). AURKA overexpression significantly enhanced the exosome-induced M2 polarization of macrophages, as evidenced by the upregulated CD163 and Arg-1, whereas AURKA knockdown suppressed this effect. Proteomic analysis revealed that lectin galactoside-binding soluble 3-binding protein (LGALS3BP) was significantly enriched in exosomes from AURKA-overexpressing HCC cells. Knockdown of LGALS3BP partially reversed the AURKA-mediated M2 polarization of macrophages.

Conclusion: AURKA in HCC cells drives M2 polarization of macrophages by upregulating exosomal LGALS3BP expression, thereby promoting the formation of an immunosuppressive tumor microenvironment in HCC. Elucidation of this mechanism provides a potential novel target for HCC immunotherapy.

Pancreatic cancer, a highly malignant tumor of digestive system, is characterized by challenges in early detection and limited therapeutic efficacy. Currently, artificial intelligence (AI) technologies—such as machine learning, deep learning, and natural language processing (NLP)—are providing innovative strategies to address key bottlenecks in the diagnosis and treatment of pancreatic cancer. Based on databases such as PubMed, Web of Science, and CNKI, this study conducted literature retrieval and screening, initially obtaining 128 articles related to AI-powered pancreatic cancer diagnosis and treatment. After in-depth review, 38 journal papers and research reports were ultimately included, covering key aspects such as AI-based disease risk prediction models, intelligent screening of medical imaging and pathological assistance diagnosis, personalized treatment strategy recommendations, efficacy monitoring, and recurrence prediction. The study systematically reviews the integration and application of AI technologies throughout the entire process of pancreatic cancer diagnosis and treatment. By conducting a meta-analysis of current practices and evidence regardin AI in pancreatic cancer diagnosis and treatment, this paper aims to provide academic references for promoting the effective translation of AI technologies into clinical practice for pancreatic cancer.

Objective: To investigate the value of dynamic changes in peripheral blood T lymphocyte subsets in predicting the efficacy and prognosis of PD-1 inhibitor combined with SOX regimen (oxaliplatin + temozolomide) in the treatment of advanced gastric cancer, and to provide a reference basis for clinical treatment effect evaluation.

Methods: A prospective study was conducted on 100 patients with advanced gastric cancer who received PD-1 inhibitor combined with SOX regimen treatment in Fudan University Pudong Medical Center and Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to December 2024. Before treatment, during the second and fourth cycles, flow cytometry was used to detect the absolute number and proportion (%) of peripheral blood lymphocyte subsets (CD3⁺T, CD4⁺T, CD8⁺T, B cells, natural killer cells), as well as the CD4⁺/CD8⁺ ratio. Enzyme-linked immunosorbent assay was used to detect the levels of serum immunosuppressive factors (soluble PD-L1, transforming growth factor-β, interleukin-6). The efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. The relationship between the dynamic changes of T cell subsets and efficacy as well as progression-free survival was analyzed.

Results: The objective response rate was 32.0% and the disease control rate was 73.0% in the entire group. There were no significant differences in baseline T-cell subsets between the two groups. Repeated measures analysis of variance showed significant time effects on the absolute count of CD8⁺ T cells and the CD4⁺/CD8⁺ ratio (P<0.001). The change in CD8⁺T cells was significantly negatively correlated with the change in soluble PD-L1 (r=-0.580, P<0.001). Survival analysis indicated that the progression-free survival time was significantly better in the high CD8⁺ T cell increase group (n=18) compared to the low increase group (n=82) (P=0.004). Multivariate COX regression confirmed that CD8⁺T cell increase was an independent prognostic factor (HR=4.588, 95% CI: 1.626-12.944, P=0.004).

Conclusion: The dynamic expansion of early CD8⁺T cells is correlated with the decrease in serum soluble PD-L1 levels, and can independently predict the efficacy and survival benefit of PD-1 inhibitors combined with chemotherapy, serving as a potential biomarker for efficacy monitoring.

Objective: To investigate the clinical application of sandwich bridging technique for constructing vascularized patches to repair large abdominal wall defects (LAWD) following abdominal wall tumor resection.

Methods: A retrospective analysis was conducted on patients who underwent bridging repair after extensive abdominal wall tumor resection. All procedures were performed by the same surgical team from Huadong Hospital Affiliated to Fudan University and Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2016 and December 2023.

Results: A total of 29 patients with LAWD after abdominal wall tumor resection were repaired using the sandwich bridging technique. Among them, 23 patients (75.9%) had type Ⅱ abdominal wall defects, and 6 patients (24.1%) had type Ⅲ abdominal wall defects. The mean tumor area was (132.1±56.3) cm², and the mean defect area was (404.5±158.6) cm². The average operation time was (250.2±99.6) min, with intraoperative blood loss of (381.0±399.2) mL. The mean follow-up period was (50.9±24.5) months. The incidence of abdominal wall hernia or bulge was 6.9%, and the incidence of incision-related complications was 17.2%.

Conclusion: The sandwich bridging technique for constructing vascularized patches is feasible for repairing LAWD caused by abdominal wall tumors.

Objective: To investigate the clinicopathological characteristics of sebaceous carcinoma (SC) and enhance the diagnostic accuracy and differential diagnosis capabilities among pathologists for this malignancy.

Methods: Clinical data from seven patients with sebaceous carcinoma (SC) were retrospectively reviewed, with comprehensive analysis of histopathological features and immunohistochemical characteristics in all cases.

Results: In this study, sebaceous carcinoma (SC) predominantly affected elderly female patients, with a median age of 65 years (male-to-female ratio = 1：2). The majority of cases (6/7) represented periocular SC, with the left upper eyelid being the most frequently involved anatomical site（5/7）. Histopathological examination revealed that all seven SC cases exhibited predominantly nested or lobulated growth patterns, intraepidermal infiltrative growth was observed in 4 cases. Variable sebaceous differentiation with additional morphological characteristics were noted. Including tumor necrosis (n=5)、ductal differentiation (n=2)、keratinization(n=2)、perifollicular growth pattern (n=2) and cystic degeneration (n=1). Immunohistochemistry showed that tumor cells were positive for epithelial membrane antigen (EMA) and androgen receptor (AR), negative for carcinoembryonic antigen (CEA), and highly expressed for nuclear associated antigen Ki-67 (Ki-67).

Conclusion: Sebaceous carcinoma (SC) represents a rare cutaneous malignancy characterized by histologically evident sebaceous differentiation. While classical SC exhibits distinctive morphological features, significant histological heterogeneity may occur. Therefore, accurate diagnosis requires comprehensive evaluation incorporating both architectural features and immunohistochemical profiling to reliably distinguish SC from its histological mimics.

Objective: To investigate the effects of tripartite motif containing 21 (TRIM21) on the proliferation, invasion and migration of pancreatic cancer cells.

Methods: Based on the Gene Expression Profiling Interactive Analysis (GEPIA) online platform, this study integrated transcriptome sequencing data and clinical prognostic data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to analyze the expression differences of the TRIM21 gene in pancreatic cancer tissues and adjacent normal tissues, as well as the correlation between TRIM21 expression levels and the prognosis of patients with pancreatic cancer. Stable pancreatic cancer cell lines (human-derived PANC-1 and mouse-derived Panc02) with TRIM21 knockdown or overexpression were constructed using siRNA interference and plasmid transfection techniques. The efficiency of TRIM21 knockdown and overexpression was verified by Western blotting. Its effects on proliferation of PANC-1 and PANC-02 cells were detected by colony formation assay, and the effects on migration and invasion of PANC-1 and PANC-02 cells were detected by wound healing assay and Transwell migration and invasion assays, respectively.

Results: The expression level of TRIM21 gene in pancreatic cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.05). High expression of TRIM21 was significantly associated with poor prognosis of patients with pancreatic cancer (P < 0.05). TRIM21 knockdown can significantly inhibit the proliferation, invasion and migration of PANC-1 and PANC-02 cells (all P < 0.05). Conversely, TRIM21 overexpression can significantly promote the proliferation, invasion and migration of PANC-1 and PANC-02 cells (all P < 0.05).

Conclusion: TRIM21 plays a tumor-promoting role in pancreatic cancer, promotes the proliferation, invasion and migration of pancreatic cancer cells, and is significantly related to the poor prognosis of patients with pancreatic cancer. The TRIM21 gene shows promise as a potential therapeutic target for pancreatic cancer.

Objective: To investigate the effects of astragalus polysaccharide (APS) on tumor growth in mice with colorectal cancer (CRC) xenografts through in vivo experiments, and to further explore the impact of APS on macrophage polarization within the tumor microenvironment and its potential mechanism of action.

Methods: A mouse xenograft model was established using murine-derived CRC CT-26 cells. The mice were treated for three weeks via intraperitoneal injection with APS, the STING inhibitor (C-176), or APS combined with C-176. A control group received an equal volume of 0.9% sodium chloride solution via intraperitoneal injection. Changes in body weight and tumor volume were monitored. After euthanasia, the tumor inhibition rate was calculated. Pathological changes in tumor tissues were assessed by HE staining, and apoptotic cells within tumors were detected by TUNEL staining. The serum levels of M2 macrophage-related factors, interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were measured by ELISA. Immunofluorescence was employed to determine the localization and expression of IL-10 and TGF-β in tumor tissues, as well as the polarization status of M1 macrophages (CD68^⁺CD11c^⁺) and M2 macrophages (CD68^⁺CD163^⁺). The mRNA and protein expression levels of colony-stimulating factor 1 receptor (CSF1R), stimulator of interferon genes (STING), and TANK-binding kinase 1 (TBK1) in tumor tissues were detected by quantitative real-time PCR and Western blotting, respectively.

Results: The CT-26 cell xenograft mouse model was successfully established. APS inhibited the growth of mouse xenografts, with a tumor inhibition rate of 27.91%. APS promoted apoptosis of tumor cells within the tumor tissue, with an apoptosis rate of 31.6%. APS downregulated the expression levels of the M2 macrophage-related factors IL-10 and TGF-β in both mouse peripheral serum and tumor interstitium (all P<0.001). Immunofluorescence results indicated that APS induced macrophage polarization towards the M1 phenotype while suppressing the polarization tendency towards the M2 phenotype. Results from quantitative real-time PCR and Western blotting suggested that APS downregulated the expression of CSF1 mRNA and protein while activating the STING-TBK1 pathway, thereby reshaping the phenotype of tumor-associated macrophages.

Conclusion: APS inhibits M2 macrophage polarization in tumor tissues of CRC-bearing mice by regulating the CSF1/STING-TBK1 signaling pathway, thereby exerting an anti-tumor effect.

Retroperitoneal sarcoma (RPS) is a rare malignant tumor originating from the retroperitoneal mesenchymal tissue. While surgical resection remains the cornerstone of curative treatment, a significant challenge is the high rate of local recurrence, underscoring the critical need for effective multimodality approaches. Radiotherapy, as an important means of local treatment, has been demonstrated to play a corresponding role in neoadjuvant, intraoperative, and adjuvant settings. Notably, preoperative radiotherapy is recommended as an effective treatment approach due to its capacity to enhance the rate of local control. Furthermore, with the continuous advancement of radiotherapy technology, proton and heavy ion therapies have shown significant advantages. Compared to traditional photon radiation therapy, they can enhance the radiosensitivity of RPS and provide better protection for organs at risk. This comprehensive review synthesizes recent evidence from landmark studies to delineate current practice patterns, analyze ongoing controversies, and highlight technological innovations shaping the radiotherapeutic management paradigm for RPS.

Objective: Investigating the influence of the nucleoprotein UHRF1 (ubiquitin-like with PHD and ring finger domains 1) on radiation radioresistance in cervical squamous cell carcinoma, and to explore its potential mechanisms.

Methods: The expression level of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) mRNA and protein in cervical squamous carcinoma parental cells (SiHa and CaSki) and radioresistant cells (SiHa-R and CaSki-R) were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The glycolytic activity of parental SiHa and CaSki cells and and analyzed cells SiHa-R and CaSki-R were analyzed through extracellular acidification rate (ECAR), glucose consumption, and lactate production assay. The specific shRNA targeting the UHRF1 gene (shUHRF1) was employed to establish UHRF1-silenced SiHa-R and CaSki-R cells by Lentivirus. Lentivirus-mediated. The effects of silencing UHRF1 expression on the radiosensitivity of SiHa-R and CaSki-R cells were evaluated using CCK-8 assays and colony formation assays. The impact on glycolytic activity in SiHa-R and CaSki-R cells was analyzed through ECAR, glucose consumption, and lactate production assays. The expression level of glycolysis-related proteins glucose transporter protein 1 (GLUT1), hexokinase 2 (HK2), and pyruvate kinase isozyme type M2 (PKM2) were examined by Western blotting. Furthermore, a xenograft mouse model was established using UHRF1-silenced SiHa-R cells, followed by ¹⁸F-FDG PET/CT imaging to evaluate tumor glucose metabolism and tumor volume after irradiation.

Results: The expression level of UHRF1 mRNA and protein were significantly upregulated in SiHa-R and CaSki-R cells compared with their parental counterparts (both P<0.01). The ECAR value, glucose uptake, and lactate production of SiHa-R and CaSki-R cells were significantly higher than those of their parental cells (all P<0.001). Silencing UHRF1 expression markedly reduced cell proliferation capacity and colony-forming capacity after irradiation (both P<0.01). Glycolytic activity was significantly suppressed, as indicated by decreased ECAR value, glucose uptake, and lactate production (all P<0.001). Consistently, the protein levels of GLUT1, HK2, and PKM2 were downregulated in UHRF1-silenced cells (all P<0.001). The ¹⁸F-FDG uptake and tumor volume in nude mice transplanted with shUHRF1 group tumors were significantly lower than those in the negative control group (shNC) (both P<0.001), tumor suppression rate was 30%.

Conclusion: UHRF1 is highly expressed in radioresistant cervical squamous cell carcinoma cells and enhances radioresistance by promoting glycolysis through upregulation of key glycolytic enzymes. Silencing UHRF1 expression significantly inhibits glucose metabolism in cervical squamous cell carcinoma cells and enhances their sensitivity to radiotherapy, suggesting that UHRF1 holds promise as a potential molecular target for improving the efficacy of radiotherapy in cervical squamous cell carcinoma.

Objective: To investigate the expression characteristics of folate receptor alpha (FOLR1) in hepatic stellate cells (HSCs) and its potential role in liver diseases, as well as to construct a mouse model with HSC-specific knockout of the FOLR1 gene.

Methods: In this study, single-cell RNA sequencing and TCGA data were used to analyze the expression patterns of FOLR1 in liver cancer tissues and HSCs. Lrat-Cre and FOLR1 flox mice constructed by CRISPR-Cas9 gene editing technology were used to generate HSC-specific FOLR1 knockout mice, and the phenotype was verified in diethylnitrosamine (DEN)+CCl₄-induced HCC model. Real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to evaluate the expression level of FOLR1 mRNA and protein in each group of mice.

Results: FOLR1 was significantly upregulated in activated HSCs and was associated with poor prognosis in HCC patients. The HSC-specific FOLR1 knockout mouse model was successfully established, with good knockout efficiency validated by PCR and sequencing. Real-time fluorescence quantitative PCR results indicated that, compared to FOLR1^fl/fl mice, the FOLR1^ΔHSC mice exhibited a 60.31% downregulation of FOLR1 mRNA expression in liver tissues induced by DEN and CCl₄ (P < 0.05). ELISA results showed a 38.32% decrease in serum FOLR1 protein concentration (P < 0.01), and immunofluorescence staining results revealed a 67.96% reduction in the area of positive FOLR1 protein staining in liver tissues (P < 0.01).

Conclusion: The HSC-specific FOLR1 knockout mouse model was successfully constructed, which provides a unique animal model platform for further exploring the possible mechanism of FOLR1 in HSCs.

Primary pulmonary lymphoma (PPL) is relatively rare malignancy in clinical practice, whose imaging and pathological phenotypes lack specificity. Traditional diagnosis primarily relies on clinicians' personal experience, which can easily lead to misdiagnosis and missed diagnoses. Machine learning (ML), as a core technology of artificial intelligence (AI), provides a new approach to improving the diagnostic efficacy of PPL. This article reviews the latest advances in ML applications for PPL diagnosis. In the field of radiomics, ML facilitates the extraction of high-throughput texture features from CT and positron emission tomography (PET) imaging to construct quantitative models, thereby significantly improving the diagnostic accuracy for differentiating PPL from lung cancer, organizing pneumonia, and other diseases. In the field of pathomics, deep learning techniques have enabled automated classification of lymphoma subtypes and objective immunohistochemical analysis. Additionally, genomics intergrated with ML helps elucidate the molecular characteristics of PPL to support its precise classification. Although the application of ML in PPL diagnosis still face challenges such as limited sample sizes, insufficient standardization and poor model interpretability, advancements in multimodal data integration, federated learning and interpretable AI are expected to propel the diagnosis and treatment of PPL toward intelligent and precise development.

Objective: To construct a unmethylated CpG (cytosine-phosphate-guanine) nano delivery system based on the cationic polymer carrier polyethylenimine (PEI), termed CpG-PEI, and to evaluate its efficiency in promoting intracellular delivery of CpG, tis ability to enhance anti-tumor immunotherapy, and its biosafety.

Methods: CpG-PEI nanoparticles were prepared through the electrostatic self-assembly method. The synthesis morphology, particle size, and zeta potential of CpG-PEI nanoparticles were characterized by agarose gel electrophoresis, field emission scanning electron microscopy, and dynamic light scattering (DLS); The uptake efficiency of CpG-PEI nanoparticles by RAW264.7 macrophages was assessed using flow cytometry and laser scanning confocal microscopy. The impact CpG-PEI nanoparticles on macrophage polarization was evaluated by detecting M1/M2 phenotypic markers on the surface of RAW264.7 macrophages via flow cytometry. The cytotoxicity and apoptosis-inducing effects of CpG-PEI nanoparticles were evaluated using the CCK-8 assay and Annexin V-FITC/PI double staining method to verify its biosafety.

Results: CpG-PEI nanoparticles with a particle size of 200−400 nm were successfully prepared, its electronegativity gradually changes towards a positive charge direction as the proportion of PEI in the synthesis system increases; CpG-PEI nanoparticles significantly enhanced the intracellular uptake of CpG by RAW264.7 macrophages and effectively induced macrophage polarization towards anti-tumor M1 phenotype. By adjusting the proportion of PEI in the CpG-PEI synthesis system, the cytotoxicity of the nanoparticles could be significantly reduced while maintaining efficient delivery and immune activation.

Conclusion: This study successfully developed a safe and effective CpG-PEI nanodelivery system, which enables efficient intracellular delivery of CpG in immune cells and induces polarization of RAW264.7 macrophages towards the anti-tumor M1 phenotype, providing a new delivery strategy for nucleic acid adjuvant-based tumor immunotherapy.

Lung cancer is one of the most common and deadly malignant tumors worldwide, with its significant tumor heterogeneity and drug resistance being major obstacles to achieving precision medicine. Patient-derived tumor organoids, which can faithfully recapitulate the genetic and pathological features of the original tumor, serve as a bridge linking basic research and clinical practice, and show great promise in advancing precision therapy for lung cancer. This paper systematically reviews the construction strategies and technical advantages of lung cancer organoid models, and points out that the key to future development lies in establishing standardized culture systems, conducting multicenter clinical validation, and deepening the integration of multi-omics data, with the aim of promoting the application of lung cancer organoids in drug development and individualized precision therapy.

Objective: This study aims to evaluate the correction effect of online adaptive radiation therapy (ART) on the setup error of patients with pelvic malignancies, analyze the impact of bladder filling status changes on setup accuracy before and after the development of ART plans, and analyze the factors related to positional changes.

Methods: A retrospective analysis was conducted on the clinical medical records of 21 patients with pelvic malignancies (including 15 cases of cervical cancer and 6 cases of prostate cancer) from September 2024 to June 2025. Using fan-beam CT three-dimensional registration technology, the setup errors in the L (Lat), X (Lng), and Y (Vrt) directions were measured before and after the ART plan was formulated. The treatment target and organs at risk (OAR) were automatically delineated by the radiotherapy planning system, and then manually modified to obtain quantitative data on bladder volume changes and target volume changes. The patients were divided into three groups: low bladder deviation change group (<40%), medium bladder deviation change group (40%-80%), and high bladder deviation change group (>80%). The influence of various factors on positional changes was analyzed.

Results: Before and after the ART plan was formulated, the setup errors in the L (Lat), X (Lng), and Y (Vrt) directions were significantly reduced from -0.62 to 0.70 cm, -1.13 to 1.36 cm, and -0.66 to 0.83 cm before the ART plan was formulated, respectively, to -0.34 to 0.17 cm, -0.22 to 0.43 cm, and -0.31 to 0.35 cm after the ART plan was formulated. The relationship between bladder filling status and setup error during the ART plan formulation period showed that as the bladder volume changes increased, the error in the abdominal-back direction would significantly increase in a short period of time, while the bladder filling status and lesion volume changes during the ART implementation were positively correlated with the patient’s positional changes.

Conclusion: ART can significantly improve the repeatability accuracy of body position and effectively reduce the inter-fraction setup error in patients with cervical cancer and prostate cancer. For patients with pelvic malignancies, highly repeatable bladder capacity (deviation <40%) is a key factor in achieving excellent body position consistency. At the same time, in the ART process, it is necessary to prioritize the assessment of bladder filling status and lesion volume changes to avoid the risks of insufficient target dose coverage and excessive OAR exposure dose caused by anatomical displacement.

Objective: To investigate the effect of overexpression of exogenous ETS translocation variant 2 (ETV2) gene on the tube-forming ability of human umbilical vein endothelial cells (HUVECs) and to construct an endothelial cell-tumor organoid co-culture model capable of adapting to tumor growth.

Methods: A doxycycline-inducible Tet-On plasmid system was used to regulate the expression level of ETV2 gene, which was transfected into HUVECs via a lentiviral vector to establish a stable transfection HUVEC cell line (named ETV2-EC) with ETV2 expression modulated by doxycycline concentration. The tube-forming ability of ETV2-EC cells induced with different concentrations of doxycycline was assessed through tube formation assay. Subsequently, ETV2-EC cells were co-cultured with breast cancer organoids, and the optimal co-culture medium for the co-culture model was determined via Calcein-AM staining and CCK-8 assay. The viability of endothelial cells and their interactions with tumor organoids in the co-culture model were observed under an optical microscope. Finally, the effect of ETV2 overexpression on the transcriptome profile of HUVECs was analyzed by RNA-seq.

Results: Induction with 10 μmol/L doxycycline significantly enhanced the tube-forming ability and tubular structure stability of ETV2-EC cells. Both endothelial cells and tumor organoids could stably survive in the breast cancer organoid culture medium containing fibroblast growth factor 2 (FGF2) and heparin. Compared with control HUVECs, ETV2-EC cells induced with 10 μmol/L doxycycline showed longer survival time, larger tubular structure area, and greater stability when co-cultured with tumor organoids. RNA-seq analysis revealed that overexpression of ETV2 gene markedly altered the transcriptomic profile of HUVECs, and the differentially expressed genes in ETV2-EC cells were mainly associated with endothelial cell proliferation, migration, and adaptation to the tumor microenvironment.

Conclusion: Overexpression of ETV2 gene in mature endothelial cells may endow them with enhanced tube-forming ability by reactivating the suppressed genes associated with lumen formation and angiogenesis. Moreover, under co-culture conditions with tumor organoids, overexpression of ETV2 gene significantly improves the survival ability of endothelial cells and their adaptation to the tumor microenvironment.

Objective: To report the first successful case of using toripalimab in combination with chemotherapy, significantly prolonging the survival of a patient with stage Ⅳ primary pulmonary choriocarcinoma (PPC), and to summarize the diagnostic and therapeutic strategies for PPC.

Methods: A case of a 64-year-old male PPC patient who progressed after receiving six cycles of concurrent chemoradiotherapy was reported. Subsequently, the patient was treated with an immune checkpoint inhibitor (ICI) in combination with the previous therapy. The efficacy was evaluated by β‌-human chorionic gonadotropin (β‌-HCG) monitoring and CT, alongside a literature review to analyze the treatment patterns.

Results: After the combination of ICI treatment, the patient’s β-HCG levels returned to normal, and the right supraclavicular lymph node metastasis was completely resolved while the hilar lung lesions remained stable, thereby extending the patient’s survival period.

Conclusion: PPC is extremely rare, with surgery and chemotherapy being the primary treatment modalities. The combination of ICIs with chemotherapy can significantly prolong the survival of patients with stage Ⅳ PPC, particularly offering new options for those who are resistant to chemotherapy.

The DNA damage response (DDR) is a series of signaling pathways activated by DNA damage. It involves DNA repair, senescence, apoptosis, and other processes, and is an important mechanism for cells to maintain genomic stability and integrity. Notably, tumor cells utilizing the alternative lengthening of telomeres (ALT) to sustain telomere maintenance exhibit persistent telomeric DNA damage and replication stress. This damage or replication stress serves a dual role. On one hand, a high level of DDR activation can facilitate telomere synthesis through homologous recombination-mediated pathways, thereby sustaining the ALT mechanism; on the other hand, excessive DDR activation may induce senescence or apoptosis in ALT cells. Consequently, ALT cells must rely on a finely-tuned regulatory system to maintain DDR activation at a moderate level, thereby balancing telomere synthesis against cell death. However, the precise regulatory mechanisms governing DDR in ALT tumor cells remain incompletely understood. This review aims to summarize the current knowledge regarding ALT-associated DDR regulatory modes and mechanisms, offering insights and a theoretical foundation for elucidating the molecular basis of ALT. Further clarification of these mechanisms holds significant implications for the development of targeted therapeutic strategies against ALT-positive tumors.

Objective: To investigate the role and potential regulatory mechanisms of iron death-related genes, such as glutathione peroxidase 2 (GPX2) and arachidonic acid 5-lipoxygenase (ALOX5), in the progression of nasopharyngeal carcinoma (NPC), and to analyse their association with immune cell infiltration.

Methods: Gene expression profiles of the GSE102349 dataset, which includes 113 NPC tissues and 154 normal nasopharyngeal tissues, were obtained from the Gene Expression Omnibus (GEO) database. Additionally, iron death-related gene information was obtained from the Ferroptosis database (FerrDb). The limma package in R software was used to identify differentially expressed genes (DEGs) in NPC tissues, followed by gene function annotation and pathway enrichment analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases using the clusterProfiler package. Ferroptosis-related genes were obtained from the Ferroptosis Database (FerrDb) and intersected with the DEGs to identify ferroptosis-related differentially expressed genes (Ferr-DEGs). A protein-protein interaction (PPI) network of Ferr-DEGs was constructed using the STRING database and visualized with Cytoscape software. Key modules within the PPI network were identified using the Molecular Complex Detection (MCODE) plugin in Cytoscape, and hub genes within these modules were screened using the cytoHubba plugin. Subsequently, gene set enrichment analysis (GSEA) was performed on the hub genes. Finally, the CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) algorithms were employed to evaluate differences in immune cell infiltration between NPC tissues and normal nasopharyngeal tissues within the GSE102349 dataset.

Results: A total of 817 upregulated and 538 downregulated genes were identified in NPC tissues. These DEGs were primarily enriched in biological processes related to immune response, apoptosis, lipid metabolism, and ferroptosis. By intersecting the DEGs with ferroptosis-related genes, a total of 26 Ferr-DEGs were obtained, including significantly downregulated GPX2 and significantly upregulated ALOX5. These Ferr-DEGs were significantly enriched in oxidative stress response, the ferroptosis pathway, the HIF-1 signaling pathway, and immune-related processes (e.g., defense response and myeloid leukocyte activation). PPI network analysis identified the top 5 hub genes: GPX2, ALOX5, heme oxygenase 1 (HMOX1), cytochrome b-245 beta chain (CYBB), and src proto-oncogene (SRC), and GPX2 and ALOX5 occupy central positions in the key modules of the PPI network. Results of GSEA pathway enrichment analysis revealed that these hub genes were significantly enriched in pathways such as the hematopoietic cell lineage, lysosome, and Fc gamma receptor-mediated phagocytosis. Results of immune infiltration analysis indicated significantly higher proportions of memory B cells, follicular helper T cells, monocytes, M0 macrophages, and activated mast cells in NPC tissues, and the infiltration levels of these cells were positively correlated with the expression levels of most hub genes (except GPX2).

Conclusion: GPX2 and ALOX5 may participate in NPC progression by regulating ferroptosis and immune cell infiltration, and are promising new therapeutic targets for NPC treatment.

Objective: To explore the influencing factors of acute radiation dermatitis (ARD) in patients with breast cancer who received radiotherapy after breast conserving surgery, so as to identify the patients who need close monitoring.

Methods: This study included 281 patients with breast cancer who received radiotherapy in the Department of Radiotherapy of the Tenth People’s Hospital Affiliated to Tongji University from January 1, 2020 to December 31, 2023 after breast conserving surgery. Clinical records were collected, and platelet counts and cytokines including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17A, TNF-a, IL-12p70, IFN-α and IFN-γ in peripheral blood were measured. The relationship between clinical pathological features, radiotherapy methods, laboratory examination indicators, and ARD was evaluated.

Results: Among 281 patients receiving radiotherapy after breast conserving surgery for breast cancer, 39 patients (13.9%) developed grade 2 ARD or higher. The results of univariate analysis showed that lymph node staging, hospitalization during radiotherapy, radiotherapy segmentation method, regional lymph node irradiation, affected breast volume, platelet count, and IL-5 level were associated with grade 2 ARD or higher. The results of multivariate logistic analysis showed that hospitalization during radiotherapy, radiotherapy segmentation method, and platelet count were independent risk factors for the occurrence of grade 2 ARD or higher (P＜0.05).

Conclusion: For patients undergoing radiotherapy in outpatient clinics, using conventional fractionation methods for radiotherapy, and having high platelet counts before radiotherapy, special attention should be paid to skin management in the irradiation area to reduce the occurrence of ARD.

Objective: To develop a tannic acid (TA) and silk fibroin (SF)-based hydrogel for paclitaxel (PTX) delivery, and to evaluate its drug-loading capacity, release performance, and inhibitory effects on breast cancer cells.

Methods: First, SF-TA hydrogel drug carriers were prepared through the interaction between TA and SF. The microstructure of the hydrogel was observed using scanning electron microscopy, while the formation mechanism of the SF-TA hydrogel was analyzed via Fourier transform infrared spectroscopy. A rheometer was employed to characterize the viscoelastic properties of the hydrogel, and the weight loss method was used to evaluate its swelling rate and water retention capacity. Subsequently, the biocompatibility of the SF-TA hydrogel with mouse skin fibroblasts L-929 cells and mouse blood cells was evaluated using the CCK-8 assay and hemolysis assay, respectively. The effect on the activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) was detected by the plate coating counting method. The in vitro degradation rate of SF-TA hydrogel was measured by the weighing method, while in vivo degradation characteristics were monitored via mouse live imaging. In vivo biosafety evaluation (including body weight monitoring, blood biochemistry testing, and blood cell counting) assessed the biocompatibility of SF-TA hydrogel. PTX-loaded SF-TA@PTX hydrogels was prepared and their PTX drug loading capacity and release characteristics were analyzed via high-performance liquid chromatography (HPLC); finally, the CCK-8 assay was employed to evaluate the SF-TA@PTX hydrogel’s effects on the survival rates of mouse mammary carcinoma 4T1 cells, human breast cancer MDA-MB-231 cells, and mammary epithelial HC11cells. The bromoindole dihydrochloride double staining method was used to assess the SF-TA@PTX hydrogel’s impact on the viability of 4T1 cells. Calcein acetoxymethyl ester (Calcein-AM)/propidium iodide (PI) double staining was employed to assess the SF-TA@PTX hydrogel’s impact on 4T1 cell activity.

Results: The SF-TA hydrogel was successfully prepared, exhibiting a loose porous structure with viscoelastic properties similar to those of human tissue. The swelling rate was found to be (34.4%±4.2%), and the hydrogel demonstrated excellent biocompatibility. It showed significant antibacterial activity, inhibiting the growth of over 90% of S. aureus and MRSA. The hydrogel exhibited excellent degradability, with rapid degradation within 6 days, and demonstrated good in vivo biosafety. The drug loading capacity for PTX was remarkable, with an encapsulation efficiency of (94.7±1.7)% and a drug loading content of (1.4±0.1)%, showing sustained and steady drug release over time, with a cumulative release of (91.2±9.6)% over 108 hours. In cell experiments, the SF-TA@PTX hydrogel significantly inhibited the proliferation of 4T1 and MDA-MB-231 breast cancer cells, effectively killing over 50% of the tumor cells.

Conclusion: The SF-TA hydrogel, as a drug delivery system for paclitaxel, exhibits high drug loading capacity, stable drug release characteristics, and significant anti-tumor cell effects, demonstrating its potential for breast cancer treatment.

DNA damage repair is a protective mechanism initiated by cells in response to genetic damage caused by endogenous or exogenous factors, playing a crucial role in maintaining genomic stability and cellular homeostasis. Factors such as ultraviolet radiation, chemicals, and ionizing radiation can induce various types of DNA damage, including single-strand breaks (SSBs), double-strand breaks (DSBs), base modifications, and intermolecular crosslinks. To ensure genetic integrity, cells have evolved a sophisticated and highly coordinated DNA damage repair system encompassing multiple repair pathways and intricate regulatory networks. In recent years, fidgetin-like protein 1 (FIGNL1) has emerged as a novel regulatory factor whose role in DNA damage repair has garnered increasing attention. Previous studies indicate that FIGNL1 plays a crucial role in homologous recombination repair, contributing to the maintenance of genomic stability. Concurrently, its abnormal expression may influence tumor cell sensitivity to chemotherapeutic agents and radiotherapy, participating in the development of treatment resistance. This review summarizes recent research on FIGNL1 in DNA damage repair and explores its potential significance in maintaining genomic homeostasis and contributing to tumor treatment resistance.

Objective: To investigate the effect of serum bile acids, especially taurochenodeoxycholic acid (TCDCA), on gemcitabine resistance and survival prognosis in patients with gallbladder cancer.

Methods: Fresh gallbladder cancer tissues from 20 patients with gallbladder cancer were selected to construct mini patient derived xenograft (mini-PDX) models and patient-derived organoids. These patients were divided into a gemcitabine sensitive group and a gemcitabine resistant group using mini-PDX drug sensitivity testing. To detect serum bile acids in gemcitabine-sensitive and gemcitabine-resistant patients with gallbladder cancer using high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and compare the differences between the two groups. Using Kaplan-Meier method and COX proportional hazards model to assess the association between serum TCDCA levels and overall survival of gallbladder cancer patients, and conducting subgroup analysis of gallbladder cancer patients based on whether they received gemcitabine treatment. In the GBC-SD cell line and gallbladder cancer organoid models, the effects of TCDCA on gemcitabine resistance were assessed using CCK-8 cytotoxicity assay, colony formation assay, and organoid drug sensitivity test.

Results: Compared with gemcitabine-sensitive group, multiple conjugated bile acids were elevated in serum from gemcitabine-resistant patients, with TCDCA showing the most pronounced increase (P=3.3×10⁻⁵). In the clinical cohort, patients with high TCDCA had significantly shorter overall survival than those with low TCDCA [hazard ratio (HR)=1.75, 95% confidence interval (CI): 1.18-2.59; P=0.009]. Subgroup analysis revealed that this adverse prognostic association was confined to patients treated with gemcitabine (HR=2.07, 95% CI: 1.23-3.47; P=0.005), whereas no significant association in those not receiving gemcitabine (P=0.338). In vitro functional assays, TCDCA treatment significantly increased the IC₅₀ of gemcitabine in GBC-SD cells, and markedly enhanced the colony forming ability of GBC-SD cells under chemotherapeutic pressure. In gallbladder cancer organoids, TCDCA similarly attenuated gemcitabine-induced growth inhibition.

Conclusion: Serum TCDCA is a potential adverse prognostic biomarker for patients with gallbladder cancer receiving gemcitabine chemotherapy. TCDCA can directly induce gemcitabine resistance in GBC-SD cells and gallbladder cancer organoids, suggesting that targeting the bile acid metabolic microenvironment may provide a feasible therapeutic strategy to reverse gemcitabine chemotherapy resistance in gallbladder cancer.

Histone deacetylase 7 (HDAC7), as a key molecule in epigenetic regulation, plays a crucial role in the initiation and progression of various tumors. Recent studies have revealed that HDAC7 not only participates in tumor cell proliferation, invasion and metastasis, but also potentially suppresses the antigen recognition capacity of immune cells by regulating the survival, maturation, differentiation and subcellular functions of immune cells such as CD4^＋ T cells, macrophages and dendritic cells. It also modulates tumor immune escape and the tumor microenvironment by suppressing immune cell activation and immune response effects through regulating the proliferation, differentiation and infiltration of immune effector cells such as CD8^＋ T cells, B lymphocytes and natural killer cells. Therefore, this review will summarize the role and related mechanism of HDAC7 in tumor immunity, and further discuss the current status of HDAC7 inhibitor applications in tumor therapy and future research directions.

Retroperitoneal soft tissue sarcoma (RPSTS) is a rare malignant tumor, and its diagnosis and treatment face significant challenges due to the high heterogeneity of the tumor. Currently, imaging examinations, such as CT and MRI, are key tools for diagnosing RPSTS. However, traditional methods have limitations in achieving precise evaluation. In recent years, machine learning technologies have shown considerable potential to further enhance the diagnosis and treatment of RPSTS. Machine learning has achieved remarkable results in subtype classification, grading, treatment monitoring, and prognostic prediction for RPSTS. For example, it can effectively distinguish different subtypes of RPSTS, such as well-differentiated liposarcoma and dedifferentiated liposarcoma, and predict important indicators, including tumor grade, treatment response, and the risk of distant metastasis. Although machine learning has made significant progress in image data processing and model optimization, the subjectivity of manual segmentation of regions of interest (ROI), the constraints of small sample data, and the “black-box” nature of deep learning models remain critical bottlenecks restricting its clinical implementation. In the future, through large-scale multicenter studies, the development of automated segmentation technologies, and improvements in model interpretability, machine learning is expected to gradually transform into a reliable clinical tool, which provides more accurate diagnostic and treatment to RPSTS patients and ultimately delivering real benefits to them.

In recent years, malignant tumors have become a major global public health issue, with mortality rate ranking second among all diseases, only after cardiovascular diseases. Tumor development is associated with multiple factors. Among them, the calcium-dependent membrane-binding protein (Copine) family, as a novel calcium-sensing protein, exhibits differential expression in various malignant solid tumors and plays a critical regulatory role in tumorigenesis and progression. Copine-7 (also known as CPNE7), a member of the Copine protein family, is significantly overexpressed in gastrointestinal tumors such as gastric and colorectal cancers, and its expression level is positively correlated with TNM stage (P < 0.01). Furthermore, high expression of CPNE7 has been confirmed to be closely associated with poor prognosis, including shortened overall survival. Further analysis reveals that CPNE7 promotes tumor cell proliferation by activating the MAPK/PI3K-AKT signaling pathway and enhances tumor cell metastatic ability by regulating the epithelial-mesenchymal transition (EMT) process. This review focuses on the latest research progress regarding CPNE7 in various malignant solid tumors, systematically summarizes the mechanisms of CPNE7 in tumor development, and aims to provide new insights and evidence for precise diagnosis and targeted therapy of tumors.

Objective: To investigate the influencing factors of radiation-induced pneumonia in patients with advanced wild-type non-small cell lung cancer (NSCLC) after receiving radiotherapy with Cyberknife, and to analyze the relationship between the expression of tissue infiltrating memory B cells (MBCs) and radiation-induced pneumonia.

Methods: Wild-type advanced NSCLC patients who received radiotherapy with Cyberknife from January 2020 to January 2022 were selected as the study subjects. A total of 128 patients with and without radiation pneumonitis were included, and their clinical medical records were collected. The number of infiltrations of tissue infiltrating MBCs were calculated, and the patients were divided into MBCs high-expression group and MBCs low-expression group according to a median expression level of 23%. The clinical characteristics of patients with and without radiation-induced pneumonia were compared. A hierarchical regression model was used to analyze the relationship between different clinical characteristics and MBCs expression. Logistic regression was used to analyze the relationship between MBCs expression and radiation-induced pneumonia. Multiple regression equations were used to analyze the relationship between MBCs expression and lung function indicators. A restrictive cubic spline model (combining spline functions with logistic regression) was used to analyze the dose-response relationship between MBCs expression and the risk of radiation-induced pneumonia, and a survival curve was constructed to analyze the impact of MBCs expression on survival.

Results: There were significant differences in age, hypertension history, diabetes history and comprehensive care between the radiation-induced pneumonia group and the no radiation-induced pneumonia group (P＜0.05). The differences in tumor location, underlying lung disease, Karnofsky performance status (KPS) score, forced expiratory volume in one second/forced vital capacity (FEV1/FVC), planned target volume (PTV), mean lung dose (MLD), volume percentage receiving 5 Gy radiation dose (V5), volume percentage receiving 10 Gy radiation dose (V10), volume percentage receiving 20 Gy radiation dose (V20), and MBCs expression were all statistically significant (P＜0.01). The results of stratified regression analysis showed that age, underlying lung diseases, and FEV1/FVC had significant negative effects on MBCs expression (P＜0.05). After excluding confounding factors with collinearity, MBC expression remained independently correlated with the occurrence of radiation pneumonitis (P＜0.05). Multiple linear regression analysis showed that the expression of MBCs was positively correlated with lung function indicators (P＜0.05). The one-year survival rates of the patients in MBCs high-expression group and low-expression group were 77.78% and 50.01%, respectively, and the two-year survival rates were 62.22% and 43.37%, respectively, both with statistically significant differences (P＜0.05).

Conclusion: There is an independent correlation between MBCs expression and radiation-induced pneumonitis. For patients with radiation-induced pneumonitis, the patients with high expression of MBCs have a higher survival rate than those with low expression of MBCs.

Objective: To establish a predictive model of platelet transfusion efficacy in patients with myelodysplastic syndrome (MDS) based on machine learning algorithms, and to validate its predictive performance and clinical utility in a patient cohort.

Methods: A total of 160 MDS patients in Yuncheng Central Hospital Affiliated to Shanxi Medical University from January 2021 to December 2024 were enrolled as the training set and divided into an ineffective group and an effective group according to platelet transfusion efficacy. Characteristic variables for constructing the prediction model of platelet transfusion efficacy in MDS patients were sequentially screened using least absolute shrinkage and selection operator (LASSO) regression analysis and logistic regression analysis. Four machine learning algorithms, namely extreme gradient boosting (XGBoost), decision tree, random forest and logistic regression, were respectively employed to construct the prediction models. Predictive performance of each model was evaluated using sensitivity, specificity, the area under the curve （AUC） of receiver operating characteristic (ROC) and Youden index. The decision curve analysis was further used to evaluate the clinical practicability of the optimal model. In addition, 73 patients with MDS in Yuncheng Central Hospital Affiliated to Shanxi Medical University and the Second Hospital of Shanxi Medical University from January to May 2025 were selected as the time validation set to evaluate the clinical generalizability of the optimal model.

Results: Among the 160 patients with MDS in the training set, the rate of platelet transfusion inefficiency was 34.38% (55/160). The proportions of fever, splenomegaly, platelet antibody positive and platelet transfusion times ≥5 times, as well as the levels of serum interleukin (IL)-1β and IL-8 in the ineffective group were higher than those in the effective group (all P < 0.05). Logistic regression analysis showed that splenomegaly, platelet antibody positive, platelet transfusion times and the levels of serum IL-1β and IL-8 were independent risk factors for ineffective platelet transfusion in MDS patients (all P < 0.05). The AUC values of XGBoost model were 0.946 [95% confidence interval (CI): 0.899-0.975] in the training set and 0.947 (95% CI: 0.868-0.986) in the validation set, which were both significantly higher than those of the random forest model [0.871 (95% CI: 0.809-0.919) and 0.830 (95% CI: 0.723-0.907)], decision tree model [0.856 (95% CI: 0.792-0.907) and 0.814 (95% CI: 0.705-0.895)] and logistic regression model [0.849 (95% CI: 0.784-0.901) and 0.804 (95% CI: 0.695-0.888)] (all P < 0.05). Additionally, in both the training and validation sets, the XGBoost model demonstrated the sensitivities of 90.91% and 91.67%, and the specificities of 89.52% and 91.84%, which were both significantly higher than those of the other three predictive models (both P < 0.05). The XGBoost model ranked the factors that increase the risk of ineffective platelet transfusion in MDS patients in order of importance, namely platelet antibody positive, platelet transfusion frequency, serum IL-8 level， serum IL-1β level and splenomegaly. The decision curve showed that when the threshold probability ranged from 0.01 to 0.99, applying the XGBoost model to predict the efficacy of platelet transfusion in MDS patients consistently demonstrates that the clinical benefits derived from correct interventions outweigh the losses caused by misjudgments, which has good clinical practical value.

Conclusion: The efficacy of platelet transfusion therapy for MDS patients is not ideal. The XGBoost model, constructed based on five clinical indicators including platelet antibody positivity, platelet transfusion frequency, serum IL-8 level, serum IL-1β level and splenomegaly, has the best comprehensive predictive performance for the platelet transfusion effect in MDS patients and has good clinical practical value. It can provide references for clinical adjustment, optimization of treatment plans and improvement of platelet transfusion efficiency.

Objective: To investigate the correlation between the expression levels of specific microRNAs (miRNAs) in macrophage-derived exosomes and the platinum-based chemotherapy efficacy and prognosis of non-small cell lung cancer (NSCLC) patients.

Methods: This study collected the clinicopathological data of all NSCLC patients who underwent radical surgery and postoperative standard first-line platinum-based chemotherapy at the Chinese People’s Liberation Army General Hospital of Northern Theater Command from January 2018 to October 2022 by reviewing the electronic medical records. All patients’ peripheral blood samples were obtained before surgery, and the exosomes were isolated from the blood samples. The expression levels of 7 miRNAs (miR-15b, miR-21, miR-27b, miR-93, miR-125a, miR-146a and miR-155) associated with macrophage phenotype differentiation were measured using quantitative polymerase chain reaction (qPCR). Based on the progression-free survival (PFS), all patients were divided into the platinum-resistant group (PFS time ≤ 6 months) and the platinum-sensitive group (PFS time > 6 months). They were also categorized into the death group and the survival group according to their survival status at the end of follow-up. Logistic regression was used to identify independent influencing factors of platinum resistance in NSCLC patients, and COX proportional hazards regression model was used to analyze independent influencing factors of poor prognosis in NSCLC patients.

Results: A total of 138 NSCLC patients were included in this study. Among them, there were 19 patients in the platinum-resistant group and 119 patients in the platinum-sensitive group. Compared with platinum-sensitive group, the proportion of patients with vascular invasion and the expression level of exosomal miR-155 in platinum-resistant group were significantly increased (both P < 0.05), while the expression level of exosomal miR-125a was significantly decreased (P < 0.05). During the follow-up period, a total of 55 patients died, and 83 patients survived until the end of the follow-up. Compared with the survival group, the proportion of patients with TNM stage Ⅲ-Ⅳ and poorly differentiated, the expression levels of serum CEA and exosomal miR-155 and miR-15b in the death group were significantly increased (all P < 0.05), while the expression levels of exosomal miR-146a, miR-21 and miR-125a were significantly decreased (all P < 0.05). The results of multiple logistic regression analysis showed that exosomal miR-125a [odds ratio(OR) = 0.647, 95% confidence interval (CI): 0.433-0.965] was an independent influencing factor for platinum resistance in NSCLC patients (P < 0.05). The results of COX proportional hazards regression analysis showed that exosomal miR-155 [hazard ratio (HR) = 1.180, 95% CI: 1.064-1.308], miR-125a (HR = 0.656, 95% CI: 0.476-0.903) and serum CEA (HR = 1.001, 95% CI: 1.000-1.002) were independent influencing factors for the poor prognosis of NSCLC patients (all P < 0.05). The area under the curve (AUC) of exosomal miR-125a for predicting platinum resistance in NSCLC patients was 0.738 (sensitivity was 53.8%, specificity was 89.5%). The combination of exosomal miR-155, miR-125a and serum CEA predicted the poor prognosis of NSCLC patients with AUC of 0.879 (sensitivity of 85.5% and specificity of 75.9%), which was superior to any single indicator.

Conclusion: The decreased expression level of miR-125a in macrophage-derived exosomes is an independent risk factor for platinum-based chemotherapy resistance in NSCLC patients. In addition, the combination of exosomal miR-155, miR-125a and serum CEA significantly enhances the predictive efficacy for poor prognosis in NSCLC patients with platinum resistance, and is expected to serve as an auxiliary reference indicator for clinical treatment decisions in NSCLC.

Objective: To investigate the effect of A disintegrin and metalloproteinase 6 (ADAMTS6) on the proliferation, migration, and ferroptosis of thyroid carcinoma (THCA) cells and its potential underlying mechanisms.

Methods: By searching bioinformatics websites and databases, the difference in the expression of ADAMTS6 gene between tumor tissues and normal thyroid tissues in the THCA dataset from The Cancer Genome Atlas (TCGA) database was analyzed, and the correlation between ADAMTS6 expression and prognosis of THCA patients as well as the correlation with the prognosis and clinicopathological characteristics of THCA patients were further analyzed. Real-time fluorescence quantitative PCR and Western blotting were used to detect the expression of ADAMTS6 in THCA and normal thyroid tissues. Western blotting was also used to evaluate the expression of ADAMTS6 in normal thyroid cells and THCA cells. TPC-1 and BCPAP cells with ADAMTS6 knockdown were constructed using siRNA technology, followed by CCK-8 assay, colony formation assay, and EdU assay to detect the effects of ADAMTS6 knockdown on the proliferation of BCPAP and TPC-1 cells, respectively, and Transwell assay to detect the effects on the migration of BCPAP and TPC-1 cells. BCPAP cells with ADAMTS6 knockdown were treated with the ferroptosis inducer RSL-3, and then CCK-8 assay was used to detect the effect on cell viability, flow cytometry was used to detect the effect on cellular lipid peroxidation, and Western blotting was used to detect the effects on the expression levels of ferroptosis-related proteins solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), and β‌-catenin protein in the Wnt/β-catenin signaling pathway. BCPAP cells with ADAMTS6 knockdown and RSL-3 treatment were further treated with the Wnt/β‌-catenin signaling pathway activator CHIR-99021, and then flow cytometry was then used to assess the effect on cellular lipid peroxidation, while Western blotting was used to detect the effects on the expression of ferroptosis-related proteins SLC7A11 and GPX-4, and β-catenin protein in the Wnt/β-catenin signaling pathway.

Results: Database analysis and Western blotting results indicated that ADAMTS6 expression was upregulated in THCA (P < 0.05). High ADAMTS6 expression was negatively correlated with overall survival (P < 0.05) and positively correlated with tumor stage and lymph node metastasis in THCA patients (all P<0.05). After ADAMTS6 knockdown, the expression levels of ADAMTS6 mRNA and protein in BCPAP and TPC-1 cells were significantly decreased (all P<0.05), and their proliferative and migratory abilities were markedly reduced (all P<0.05). Treatment of ADAMTS6-knockdown BCPAP cells with RSL-3 further reduced the ferroptosis resistance of BCPAP cells to and promoted cellular lipid peroxidation (all P<0.05). Western blotting results showed that, compared with control cells, the expression levels of SLC7A11, GPX4, and β‌-catenin proteins in BCPAP cells were significantly decreased after ADAMTS6 knockdown (all P<0.05). The Wnt activator CHIR-99021 upregulated the expression levels of GPX4, SLC7A11, and β‌-catenin proteins in ADAMTS6-knockdown BCPAP cells treated with RSL-3 (all P<0.05), while lipid peroxidation decreased (all P<0.05).

Conclusion: ADAMTS6 is highly expressed in THCA tissues and its high expression is associated with poor prognosis in patients. Knockdown of ADAMTS6 inhibits the proliferation, migration, and ferroptosis resistance of THCA cells, and the underlying mechanism may be related to the downregulation of Wnt/β‌-catenin signaling pathway activity.

Objective: To investigate the structural characteristics of invadopodia in pancreatic cancer cells.

Methods: The formation of invadopodia in low invasive pancreatic cancer PANC1 cells and high invasive pancreatic cancer BXPC3 cells was observed under laser confocal microscope after immunofluorescence staining, and the relationship between the formation of invadopodia and proteolytic function was studied through gelatin matrix degradation experiment. Transforming growth factor-β (TGF-β) was used to treat pancreatic cancer BXPC3 cells, and gelatin matrix degradation test and immunofluorescence test were used to detect the effect of TGF-β on the formation of invadopodia of BXPC3 cells; The real-time fluorescence quantitative PCR was used to detect the effect of TGF-β on the mRNA expression of matrix metalloproteinases (MMP)-1 and MMP-9 in BXPC3 cells. Finally, a higher resolution structured illumination microscope (SIM) was used to reconstruct the three-dimensional structure of the invadopodia of BXPC3 cells, further exploring its spatial structural characteristics.

Results: Through immunofluorescence experiment, it was found that in high invasive pancreatic cancer BXPC3 cells, scattered single dot like invadopodia could be formed, and special rosette ring structure could also be formed. However, in low invasive pancreatic cancer PANC1 cells, there was no such obvious invadopodia feature. The invadopodia formed in BXPC3 cells were related to the function of matrix degradation, and the number of invadopodia was increased after stimulation by TGF-β, and the expression level of MMP-9 mRNA was up-regulated (P<0.000 1), thus increasing the proteolytic activity of cells. The three-dimensional structure of invadopodia in BXPC3 cells was further reconstructed using SIM.

Conclusion: Based on laser confocal microscopy and SIM, the structural characteristics of invadopodia in pancreatic cancer cells were preliminarily observed and described, and the effects of TGF-β on the formation and function of invadopodia in pancreatic cancer cells were explored.