Objective: To investigate the characteristics of human epidermal growth factor receptor 2 (HER2) protein expression and gene status in uterine serous carcinoma (USC) patients. Methods: A total of 36 formalin-fixed and paraffin-embedded USC tissue specimens obtained between 2021 and 2022 in Peking Union Medical College Hospital were collected. The expression of HER2 protein and the gene status were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) respectively, and the results were interpreted according to the 2020 International Society of Gynecological Pathologists recommendations. Results: Among the 36 cases, 11, 8, 12 and 5 cases showed HER2 IHC scores of 0, 1+, 2+, and 3+, respectively. All IHC 3+cases were pure USC. Out of 25 samples with different level of HER2 expression (IHC 1+, IHC 2+and 3+), 16 (64.0%) tumors with heterogeneous stain, which mainly affects the diseases with IHC 2+ (10/12) and IHC 3+ (3/5) lesions. Ten pure USC cases (27.8%, 10/36), involving HER2 IHC 0, IHC 1+, IHC 2+and IHC 3+tumors, harbored HER2 gene amplification by FISH (1, 1, 3 and 5 cases, respectively). All amplified cases exhibited a HER2/CEP17 ratio≥2.0. In addition, the incidences of chromosome 17 (CEP17) polysomy and monosomy were 25.0% (9/36) and 19.4% (7/36), respectively. Conclusions: Most of USC tumors exhibit intratumoral heterogeneity in HER2 IHC stain. Both HER2 IHC positive (3+) and FISH positive occur exclusively in pure USC tumors. HER2 gene amplification can be observed in any HER2 IHC levels.

Objective: To investigate the clinicopathological features, molecular characteristics and differential diagnosis of extraskeletal myxoid chondrosarcoma (EMC). Methods: A total of 16 cases of EMC diagnosed from January 2016 to February 2025 were collected from Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital, 3 cases) and Beijing Jishuitan Hospital, Capital Medical University (13 cases) for clinicopathological, immunohistochemical, fluorescence in situ hybridization (FISH) and next generation sequencing analyses and follow-up. Results: There were 11 males and 5 females, with a median age of 51(30, 73) years. The tumor sites included extremities (n=12), trunk (n=3), and sacrum (n=1). Histologically, EMC showed two distinct subtypes. Fourteen cases (14/16) were classic subtype with pale-blue myxoid or chondromyxoid matrix. The cells characteristically interconnected with one another to form cords, small clusters, and complex trabecular or cribriform patterns. The tumor cells were round, ovoid, short spindle or star-shaped; some may be rhabdoid with eosinophilic cytoplasm and eccentrically placed nuclei. Two cases were cellular subtype, demonstrating solid sheets of epithelioid cells with minimal intervening myxoid matrix, large vesicular nuclei, prominent nucleoli, and brisk mitotic activity. Immunohistochemistry showed that the cells diffusely or partially expressed vimentin, CD117, Syn, INSM-1, CD34, SMA and NSE, but were negative for pan-keratin (AE1/AE3), S-100, calponin, desmin and brachyury. INI1 expression was not deleted. The proliferation index of Ki-67 ranged from 2% to 15% in the classic subtype and 5% in the cellular subtype. NR4A3 gene rearrangement was detected by FISH in 15 cases (15/16), and EWSR1::NR4A3 fusion was confirmed by next-generation sequencing in 4 cases. Follow-up data were available in 14 patients (1-104 months), of whom 7 (7/14) developed local recurrence and 2 (2/14) developed distant metastases. Conclusions: EMC is a rare mesenchymal malignancy that arises not only in soft tissues but also in bone. The predominant histological subtype is classical EMC, with a minority presenting as cell-rich EMC. FISH detection of NR4A3 gene rearrangements provides a crucial value for the diagnosis. It needs to be differentiated from myoepithelial tumors, chordomas and myxoid liposarcomas.

Objective: To investigate the clinicopathological and prognostic features, immunophenotypic characteristics, and key points of differential diagnosis of multifocal EBV-associated smooth muscle tumors (EBV-SMT). Methods: The clinicopathological data of 7 cases of EBV-SMT diagnosed in Sun Yat-sen University Cancer Center from June 2020 to March 2025 were retrospectively analyzed. Immunohistochemical staining, Epstein-Barr virus-encoded small RNAs (EBERs) in situ hybridization, and next-generation sequencing were performed, and the relevant literature was reviewed. Results: All 7 patients were children or young adults, with a median age of 7 (2, 33) years. Five patients were immunocompromised due to congenital immune deficiency, autoimmune disease or post-transplant treatment. All the 7 cases presented with multifocal lesions, involving the brain, liver, lungs and adrenal glands. Histologically, 3 cases exhibited a classic spindle cell leiomyoma-like morphology, while the other 4 showed a more primitive round cell morphology resembling smooth muscle cells. All cases expressed smooth muscle markers, such as SMA, calponin, HHF35, h-caldesmon, and desmin, among others. The proliferation index of Ki-67 ranged from 1% to 30%. All cases were diffusely and strongly positive for EBERs by in situ hybridization. Next-generation sequencing identified an ITK gene deletion in one case (case 2). During a follow-up period of 1 to 44 months after diagnosis, 2 patients died, while the remaining 5 survived. Conclusions: EBV-associated smooth muscle tumors are more likely to occur in children or young adults with immune deficiency, often manifesting as multifocal lesions in different organs. Accurate diagnosis relies on a comprehensive assessment incorporating clinical history, histopathological features, and findings of immunohistochemistry and EBERs in situ hybridization.

Objective: To study the clinical and pathological features of anaplastic sarcoma of the kidney(ASK) in children, and to explore its molecular profiles and differential diagnosis. Methods: Five cases of pediatric ASK diagnosed at Beijing Children's Hospital, Beijing, China from January 2018 to June 2025 were collected. The clinical, histological, and immunohistochemical features were analyzed. Three cases were subjected to TP53 detection using fluorescent in-situ hybridization (FISH), and DICER1 and TP53 detection using PCR amplification and Sanger sequencing. Results: There were 3 males and 2 females. The patients' ages ranged from 1.6 years to 17.7 yeas, with an age of 8.2 (3.8, 12.7). A renal mass was accidentally found in 1 case, and abdominal pain with hematuria was present in 4 cases. Four cases were presented as a unilateral tumor, while one as bilateral tumors. The radiographic features of ASK were cystic and solid masses. The tumors were staged as stage Ⅰ, Ⅴ, Ⅳ, Ⅱ and Ⅱ, respectively. Histologically, all tumors showd both cystic and solid areas, spindle cell components with anaplastic changes and frequent atypical mitotic figures, arranged in a fascicular pattern. Chondroid differentiation and rhabdomyoblasts features were present. Multiloculated cysts showed cystic nephroma-like foci, and subepithelial primitive cells with cambium-like layer appearance. Immunohistochemistry showed that desmin was positive in 3 of the 5 cases, and myogenin and MyoD1 were positive in 2 of the 5 cases. p53 was overexpressed(mutated type) in 2 cases, loss of expression(null type) in 1 case and wild type in 1 case. Ki-67 positive rates were 30%-90%. Three cases with sequencing information harbored DICER-1 mutations(somatic and truncating mutations) and loss of TP53 gene. One patient with bilateral tumors died during follow-up. Another patient had distant metastasis, while the others had no recurrence or metastasis. Conclusions: ASK in children is a rare DICER1-related tumor, with distinct histologic features and biological behavior. The differential diagnosis includes anaplastic Wilms tumor, clear cell sarcoma of the kidney, etc. Integration of clinical manifestations, histology, immunohistochemistry, and molecular studies may be required to render correct diagnosis.

Objective: To investigate the clinicopathological features and molecular genetic alterations of the YWHAE-rearranged clear cell sarcoma of the kidney (CCSK), and to improve the diagnostic and differential diagnostic accuracy of the subtype of renal clear cell sarcoma. Methods: A retrospective analysis was performed on 7 cases of YWHAE-rearranged CCSK diagnosed and treated at the Shanghai Children's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China and the Children's Hospital of Fudan University, Shanghai, China between January 2018 and October 2023.Their clinicopathological characteristics were analyzed using HE staining, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Patient survival was assessed based on follow-up data. Results: Of the 7 patients with YWHAE-rearranged CCSK, 4 were male and 3 were female, aged 1.0-7.0 years, with an age of 2.0 (1.6, 6.0) years. The primary symptom was predominantly an abdominal mass (6 cases), with 1 case presented with abdominal pain and vomiting. All tumors were unilateral (left side in 3 cases, and right side in 4 cases). Preoperative imaging suspected Wilms tumor in all cases. Histologically, the classic type (4/7) and spindle cell type (2/7) were predominant while one case showed a mixed classic and epithelioid pattern. Vascular invasion was present in 3 cases, and lymph node metastasis was identified in 1 case. IHC results showed diffuse positivity for cyclin D1, bcl-2, and SATB2 in all cases, with varying expression of BCOR. FISH with break-apart probes analyses confirmed YWHAE (17p13) gene fusions in all cases. NGS performed in 2 cases revealed the presence of YWHAE::NUTM2 fusions, accompanied by mutations in FBXW7 or CREBBP gene. There were 5 Stage-Ⅲ cases and 2 Stage-Ⅳ cases. Postoperative follow-up ranged from 20 to 69 months and showed 3 patients with metastasis or recurrence. One of them also developed chronic renal failure. Conclusions: YWHAE-rearranged CCSK exhibits morphological heterogeneity and aggressive behaviors. Definitive diagnosis relies on molecular testing (such as FISH or NGS), which is crucial for differential diagnosis and prognostic evaluation. This subtype of CCSK is commonly associated with advanced clinical stage and early metastasis/recurrence, highlighting the necessity for improving risk stratification and clinical management.

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics and prognosis of acquired cystic disease-associated renal cell carcinoma (ACD-RCC). Methods: The clinicopathological data of four ACD-RCC cases diagnosed at the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China and one case at the Ningbo Clinical Pathology Diagnostic Center, Ningbo, China between 2018 and 2025 were collected. The clinical, histological, and immunohistochemical characteristics were analyzed. FISH and high-throughput DNA targeted next generation sequencing (NGS) were carried out. Follow-up was conducted with review of relevant literature. Results: Among the five patients, four were male and one was female, aged 45-71 years. All patients had a history of chronic kidney disease (duration 9-30 years) and received dialysis treatment. Three cases occurred in the right kidney and two in the left kidney. All were single lesions with a maximum diameter of 2.0-15.0 cm. Grossly, the tumors showed a solid-cystic appearance. Histologically, various histological patterns were observed, including cystic (4 cases), tubular (4 cases), papillary (4 cases), solid (2 cases), cribriform (2 cases), and microcystic structures (1 case). Two cases were accompanied by tumor necrosis, and one case was accompanied by sarcomatoid differentiation. The tumor cells had abundant eosinophilic cytoplasm with intracytoplasmic vacuoles, conspicuous nucleoli, and high nuclear grades (World Health Organization/International Society of Urological Pathology nuclear grade 3 or 4). Two cases had focal, clear cytoplasm. Oxalate crystals were present in all tumors. In all cases, the surrounding renal parenchyma was atrophic with multiple cysts. The cysts in three cases were lined by single-or multiple-layered eosinophilic cells, which had abundant cytoplasm and visible nucleoli. Tumor cells in all five cases expressed PAX8, CD10 and P504s. Two cases partially expressed carbonic anhydrase Ⅸ(CAⅨ). Two cases focally expressed CK7, CD117, HMB45, Melan A, TFE3, TFEB, GATA3, 2SC and ALK were negative in all cases. FH, SDHB and SMARCB1 (INI1) proteins were not deficient. TFE3 gene rearrangement was not detected in two cases using FISH with break-apart probes. High-throughput DNA targeted NGS showed that one tumor had a KMT2C mutation, one had KMT2B, TSC1, SETD2 and TP53 mutations, one had an MTOR mutation, one had a TSC2 mutation, and one had an SETD2 mutation. The five cases were followed up for 6-70 months and had no recurrence or metastasis, except one case with local recurrence and retroperitoneal lymph node metastasis four years after the surgery. Conclusions: ACD-RCC is a rare renal cell carcinoma that occurs in patients with end-stage renal disease and has unique morphological features. It is often associated with favorable prognosis and alterations in genes related to the MTOR/TSC pathway or chromatin modification.

Objective: To investigate the characteristics of germline/somatic homologous recombination repair (HRR) gene variants in patients with hormone-sensitive prostate cancer (HSPC) and to analyze their associations with clinicopathological features. Methods: A retrospective study was conducted on 108 clinicopathologically high-risk HSPC patients diagnosed at the Peking University Third Hospital, Beijing, China from 2019 to 2022. Next generation sequencing (NGS) was used to simultaneously detect germline and somatic gene variants (32-98 genes, including at least 19 HRR-related genes). The HRR gene variation profiles were characterized. Their correlations with clinicopathological characteristics were analyzed. Results: Genetic mutations were found in 23 patients, the age ranged from 36 to 83, with an age of 66(56,68)years. Germline HRR gene variants were detected in 4 (3.7%, 4/108) of the 108 patients, with BRCA2 being most common (1.9%, 2/108), followed by PALB2(0.9%)/RAD51D(0.9%). Somatic HRR gene variants were identified in 14 patients (13.0%, 14/108), involving 17 variants (affecting BRCA1/BRCA2/ATM/CDK12/FANCA). CDK12 was the most frequently mutated gene. Among these 14 patients, 3 had two different variants (either in different genes or two distinct variants in the same gene). In addition to the most common point-mutations and small insertions/deletions, copy number loss of BRCA1 was detected in 1 case. Non-HRR-related gene variants were identified in 5 patients. Among them, 3(2.8%) had TP53 variants (1 case had mixed acinar and ductal adenocarcinoma) and 2 had PTEN and KRAS mutations. Compared with the patients without gene variations, the ones with somatic HRR gene variations were younger, presented with higher serum total prostate-specific antigen (PSA) levels and more advanced tumor stage (all P<0.05). No significant correlations were observed between somatic HRR gene variants and free PSA levels or grade groups (P>0.05). Conclusions: HSPC exhibits high genetic heterogeneity. BRCA2 is the most common gene with germline variations, while CDK12 is the most frequently mutated gene in somatic HRR variants. This study suggests that HRR gene testing in patients with high-risk HSPC would help identify those with more aggressive clinical features and guide prognostication and potential targeted therapeutic strategies.

Renal cell carcinoma with tumor thrombus is a subtype of urinary system malignancy with high clinical challenges. In recent years, with the development of pathological techniques and growing insights into molecular mechanism research, significant progress has been made in the fields of molecular regulation of tumor thrombus formation, precise pathological assessment, and optimization of staging systems. This article focuses on the pathological features of renal cell carcinoma with tumor thrombus, systematically sorts out the application differences of the clinical staging and grading system of tumor thrombus, explores the impact of pathological assessment on clinical staging, treatment strategy selection and patient prognosis, and analyzes the formation mechanism of tumor thrombus from the perspectives of relevant molecular and cellular ecology.

Circulating tumor cells （CTC） have emerged as crucial mediators in the metastatic cascade， offering invaluable insights as real-time liquid biomarkers for cancer progression， prognosis， and treatment response. Their exceptionally low concentration in peripheral blood， which typically ranges from a handful to a few dozen cells per milliliter amidst billions of background blood cells， poses formidable challenges for isolation and molecular characterization. Despite this， the efficient and specific capture of CTC holds tremendous potential for revolutionizing early cancer detection， dynamic monitoring of therapeutic efficacy， and guiding personalized treatment strategies. Currently， the primary technologies for CTC enrichment fall into two categories： immunoaffinity-based methods that employ antibodies targeting epithelial surface markers such as epithelial cell adhesion molecule （EpCAM）， and label-free approaches that leverage physical properties including cell size， deformability， and density， exemplified by membrane filtration and centrifugal techniques. However， these conventional methods are hampered by several inherent limitations， including high operational costs， dependence on highly variable surface antigen expression， insufficient capture specificity leading to low purity， and significant interference from heterogeneous blood components such as leukocytes and platelets. Consequently， there is an urgent and growing need to develop novel functional materials and platforms that offer enhanced selectivity， robust stability in physiological conditions， excellent biocompatibility， and improved clinical applicability for the effective isolation and analysis of CTC. In this study， we innovatively integrate cell imprinting technology with a rational amino acid-based affinity strategy to develop a tryptophan-histidine-arginine （WHR） tripeptide-functionalized cell-imprinted hydrogel for highly efficient and selective capture of CTC. The design leverages the unique properties of mesoporous silica nanoparticles （MSN） as carriers， which are first synthesized and then surface-modified with epoxy groups via silane coupling agents. The WHR tripeptide is subsequently grafted onto the MSN surface through a ring-opening reaction， yielding the WHR@SiO₂ composite material. This material demonstrates strong and specific binding affinity toward sialic acid （Neu5Ac） and sialylated glycopeptides （SGP）， which are overexpressed on the surface of many cancer cells. Building on this molecular recognition capability， a three-dimensional cell-imprinted hydrogel is fabricated using poly（ethylene glycol） dimethacrylate （PEGDMA） as the cross-linking backbone via free radical polymerization. The hydrogel is molded against SMMC-7721 template cells to create cavities that complement the target cells in size， shape， and surface topology， thereby enhancing capture efficiency through both physical and biochemical matching. Experimental results demonstrate that the WHR-modified hydrogel achieves a remarkable capture efficiency of up to 94% for SMMC-7721 cells， significantly outperforming hydrogels modified with individual amino acids such as tryptophan， histidine， or arginine alone. The system also exhibits excellent hemocompatibility， with minimal adsorption of human serum albumin （HSA）， below 5%， indicating superior anti-fouling properties in biological environments. In vitro cytotoxicity assessments confirm high biocompatibility， with cell viability exceeding 90% after 48 h of co-culture. Further characterization through scanning electron microscopy （SEM） and atomic force microscopy （AFM） reveals well-defined surface imprints that mirror the morphology of template cells， confirming the successful integration of topographical cues. The synergy between the physical structure of the imprinted cavities and the biochemical affinity of the WHR tripeptide is identified as the key factor contributing to the high capture performance， even at low cell concentrations （as few as 100 cells/mL）. In conclusion， this work presents a robust and efficient platform for CTC capture that combines cell imprinting for morphological recognition with WHR-mediated affinity for sialylated glycoproteins. The hydrogel demonstrates high selectivity， stability， and biocompatibility， offering a promising tool for clinical applications in liquid biopsy and early cancer detection. The modular design of the system also allows for adaptation to other cancer types by altering the peptide sequence or template cells， highlighting its broad potential in cancer research and diagnostics.

To explore the molecular mechanism by which cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) agonists enhance cytotoxicity of natural killer (NK) cells against gastric cancer cells.

To investigate the expression of membrane protein palmitoylated 6 (MPP6) in hepatocellular carcinoma (HCC) and analyze its correlation with clinicopathological features and patient prognosis and its impact on biological behaviors of HCC cells.

To explore the molecular mechanisms by which quercetin regulates proliferation, migration, and apoptosis of gastric cancer cells.

Molecular docking was employed to analyze the binding affinity between the active components of YQJDF and AKT1. MTT assay, real-time cell analysis (RTCA), wound healing assay and Matrigel invasion chamber assay were used to evaluate the effect of YQJDF extract on proliferation, migration and invasion abilities of human NPC cell lines 5-8F and 6-10B, and the changes in cellular protein expression levels were detected using Western blotting. In a BALB/c nude mouse model bearing NPC cell xenografts, tumor growth were observed following treatment with daily gavage with normal saline or YQJDF extract (15.357 g/kg) for 18 consecutive days or with intraperitoneal injections of 5-Fu every other day. The changes in the expressions of AKT1/GLUT1 signaling axis proteins in the xenografts were examined using Western blotting.

To explore the key technical points and value of cell transfer technology in the diagnosis of micro-volume cell fluid.

To explore the gross classification of gallbladder cancer with primary lesion confined within the gallbladder wall, and its correlation with prognosis and precancerous lesions.

Objective: To compare the clinical efficacy and safety of robot-assisted navigation systems with those of the conventional puncture localization method in CT-guided percutaneous lung biopsy. Methods: We retrospectively collected clinical data from 140 patients who underwent CT-guided percutaneous lung biopsy at the Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, from January 6, 2021 to April 23, 2024. Among them, 103 patients were assigned to the manual operation group and 37 patients to the robot-assisted group. Propensity score matching was used to match the baseline characteristics of the two groups, with 29 patients included in each group for final analysis. Puncture time, procedure time, number of needle adjustments, number of CT scans, and incidence of complications were compared between the two groups. Results: After propensity score matching, the mean puncture time in the robot-assisted group was 6.59 minutes shorter than that in the manual operation group (15.72 min vs. 22.31 min, supplementary test value, P=0.012), and the mean procedure time was reduced by 4.99 minutes (24.62 min vs. 29.62 min, supplementary test value, P=0.069). The mean number of needle adjustments (1.03 vs. 2.69, supplementary test value, P=0.002) and the mean number of CT scans (4.31 vs. 6.55, P<0.001) in the robot-assisted group were both significantly lower than those in the manual group. Stratified analysis based on lesion location and size showed that for lower lung lesions, the mean puncture time was significantly shorter than that in the manual group (28.78 min vs. 16.6 min, P=0.04). For lesions larger than 30 mm, the mean puncture time (22.11 min vs. 12.92 min, P=0.006), number of needle adjustments (2.92 vs. 0.83, P<0.001), and number of CT scans (6.63 vs. 3.80, P<0.001) were all lower than those in the manual group, with statistically significant differences. Additionally, in the robot-assisted group, 7 patients (24.1%) used an out-of-plane needle positioning method, with intraoperative mean puncture time, procedure time, mean number of needle adjustments, and mean CT scans of 15.86 min, 23.71 min, 0.86, and 4.29, respectively. The incidence of bleeding complications in the robot-assisted group was lower than that in the manual group. Conclusions: Compared with the manual operation group, the robot-assisted group exhibited shorter mean puncture and procedure times, fewer needle adjustments and CT scans, a shorter mean puncture time for lower lung lesions, reduced mean puncture time along with fewer needle adjustments and CT scans for lesions larger than 30 mm, and a lower incidence of intraoperative bleeding.

Liver nodules are one of the common and complex clinical conditions, with certain ones developing into malignant lesions, hence significantly affecting patient prognosis. The detection rate of liver nodules has significantly improved with advances in modern imaging technology; however, there is still a lack of unified guidance on their diagnosis, treatment, and management. The "Expert Consensus on the Diagnosis, Treatment, and Management of Liver Nodules (version 2026)" systematically summarizes and standardizes aspects of liver nodules, including definition, classification, screening, diagnosis, treatment, and follow-up, through multidisciplinary collaboration based on the latest domestic and international research findings and expert clinical experience. This article emphasizes the importance of multidimensional assessment for liver nodules, including quantity, size, liver imaging reports, classification in data management systems, and pathological type. The implementation of individualized screening in high-risk populations is recommended at least once every six months starting at age 40, while for those with liver cirrhosis, malignant liver nodules, or a family history of liver cancer, screening should begin at age 30. The diagnostic strategy integrates systematic medical history, physical examination, imaging, and the detection of multiple serum marker collections. The usage of scoring models such as aMAP, GALAD, and GAAD highlights the diagnostic value of liver pathology and advocates a multidisciplinary team approach for risk assessment. Treatment plans emphasize individualization and involve etiological treatment, surgical therapy, interventional therapy, radiotherapy and systemic therapy. The aim of this consensus is to standardize the diagnosis and treatment of liver nodules, enhance precision, implement graded management, enable early differentiation between benign and malignant liver nodules, and improve patient prognosis.

Stage III non-small cell lung cancer (NSCLC) accounts for approximately 30% of newly diagnosed NSCLC cases, and the vast majority of these patients present with unresectable disease. Its unresectable nature makes definitive chemoradiotherapy the cornerstone of treatment. In recent years, with immune checkpoint inhibitors (ICIs) becoming a major research focus in lung cancer, increasing evidence demonstrates that the combination of radiotherapy and immunotherapy (iRT) can significantly enhance antitumor efficacy through synergistic mechanisms. The groundbreaking results of the landmark PACIFIC trial further established consolidation immunotherapy following concurrent chemoradiotherapy as the standard of care. However, controversies persist regarding optimal radiotherapy strategies, timing of immune intervention, management of adverse reactions, and exploration of biomarkers. This review aims to systematically elucidate the synergistic mechanisms of iRT, summarize clinical trial advances under different iRT treatment modalities (concurrent, consolidation and induction), and provide an in-depth analysis of key issues in current clinical practice along with future research directions.
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Lung cancer, one of the leading causes of cancer-related deaths worldwide, severely influences patients' quality of life and prognosis due to its complication of brain metastasis (primarily involving the brain parenchyma). While traditional treatments such as surgery, radiotherapy, and chemotherapy have demonstrated efficacy in clinical practice, their application remains limited due to toxicity and patient tolerance issues. Emerging targeted therapies and immunotherapies, which exhibit significant efficacy with fewer side effects, still face challenges including partial drug resistance and genetic mutations. In recent years, research on the association between gut microbiota and lung cancer brain metastasis has gained prominence. Its mechanism of action may influence the progression of brain metastasis through multidimensional interactions via the brain-gut axis, involving neuroendocrine and immune pathways. This review examines specific mechanisms by which gut microbiota modulate lung cancer brain metastasis through immune regulation, endocrine-metabolic regulation, and neurotransmitter control via the brain-gut axis, as well as therapeutic and traditional medicine research on regulating gut microbiota in lung cancer brain metastasis. It aims to provide theoretical support and identify potential clinical therapeutic targets for the prevention and treatment of lung cancer brain metastasis.
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Lung cancer is the malignant tumor with the highest morbidity and mortality, and it is usually diagnosed with advanced metastasis. Tumor metastasis is an important factor affecting treatment resistance and poor prognosis of lung cancer, among which bone metastasis is a common metastatic pattern of lung cancer and is associated with a particularly dismal prognosis. Meanwhile, bone metastasis frequently causes skeletal-related events such as bone pain, pathological fractures, nerve compression, and hypercalcemia. Exosomes are extracellular vesicles with a diameter of 40-160 nm that are released from the fusion of intracellular multivesicular bodies and the cell membrane. Carrying proteins, lipids, and nucleic acids, they mediate communication between tumor cells and their surrounding matrix, immune cells, and the bone microenvironment. So, it has attracted increasing attention from researchers. This paper aims to summarize and organize the latest research advances on exosomes promoting lung cancer bone metastasis, focusing on their key mechanisms and signaling pathways. These include promoting tumor cells proliferation, invasion and metastasis at the primary lesion, as well as participating in energy metabolism reprogramming, pre-metastatic niche remodeling, immune microenvironment regulation, and interactions with osteocytes, stromal cells, and other cells during distant bone metastasis colonization. In addition, this review analyzes the potential clinical translational value of exosomes in the early diagnosis, treatment, and prognosis of lung cancer bone metastasis.