ABSTRACT Background Advanced ovarian cancer often presents with extensive pelvic and abdominal metastases, even malignant pleural effusion. Consequently, multivisceral resection has become the common surgical approach to achieve optimal resection of ovarian cancer. The present study aimed to evaluate postoperative complications and prognosis of multivisceral resection performed by the independent gynecologic oncologist team (GOT) or multidisciplinary team (MDT). Methods The retrospective cohort study enrolled ovarian cancer patients who underwent surgery with multivisceral resection in Jiangsu Cancer Hospital. Patients were divided into two groups depending on the surgical team: the GOT and MDT groups. Patient baseline characteristics, surgical outcomes, postoperative complications, and long‐term prognosis were compared between the GOT and MDT groups. Results Between January 2017 and June 2024, 299 ovarian cancer patients were included in this study: 83 in the GOT and 216 in the MDT group. The GOT group had shorter operating times (235 vs. 290 min; p < 0.001) and less blood loss (400 vs. 600 mL; p < 0.001) compared with the MDT group. There were no significant differences in postoperative complications and median progression‐free survival (PFS) (not reached (NR) vs. 22.8 months; HR = 0.818, 95% CI 0.507–1.320; p = 0.410) between the GOT and MDT groups. In multivariate analysis, HRD positive status was an indicator of a favorable prognosis (HR = 0.453; 95% CI 0.243–0.844; p = 0.013). Conclusion The results suggest that ovarian cancer patients who underwent multivisceral resection performed by the independent gynecologic oncologist team are safe and feasible. Our team will continue to follow up to obtain more comprehensive survival data to validate this finding.

OBJECTIVES:Induction immunochemotherapy is the standard of care for resectable stage II and III non-small cell lung cancer. However, the comparative effectiveness of subsequent definitive surgery versus radiotherapy remains uncertain. We aimed to compare outcomes between these 2 strategies in routine clinical practice. METHODS:This multicenter, retrospective cohort study included patients with stage II and III non-small cell lung cancer who received induction immunochemotherapy followed by surgery or definitive radiotherapy across 12 centers in China. Propensity score matching (1:2) was used to balance clinicopathological characteristics. The primary end point was progression-free survival; secondary end points included overall survival and recurrence patterns. RESULTS:Among 967 patients (683 surgery; 284 radiotherapy), the matched intent-to-treat cohort included 548 patients (365 surgery; 183 radiotherapy). Compared with radiotherapy, surgery was associated with significantly longer progression-free survival (hazard ratio, 0.32; 95% CI, 0.23-0.44; P < .001) and overall survival (hazard ratio, 0.41; 95% CI, 0.26-0.66; P < .001). Surgery reduced overall recurrence (-21.3%; 95% CI, -31.1 to -11.3) and local recurrence (-17.5%; 95% CI, -25.0 to -9.9), but did not affect distant metastasis. In the subgroup of patients for whom pneumonectomy was indicated, surgery improved progression-free survival (hazard ratio, 0.47; 95% CI, 0.26-0.85; P = .013) but did not confer an overall survival benefit (hazard ratio, 1.14; 95% CI, 0.48-2.70; P = .76). Among patients who achieved a clinical complete response, outcomes were similar between the 2 groups. CONCLUSIONS:Definitive surgery after induction immunochemotherapy offers superior progression-free survival and overall survival compared with definitive radiotherapy, primarily driven by improved local control. For patients requiring pneumonectomy or achieving a clinical complete response, treatment should be individualized, and prospective trials are warranted.

BACKGROUND:The tumor and node metastasis (TNM) staging and pathological grading systems are currently insufficient for accurately predicting recurrence-free survival (RFS) in patients with pathological stage (p-stage) I lung adenocarcinoma (LUAD). Therefore, there is an urgent need for a more economical and applicable clinical prediction model to assess the risk of recurrence and guide clinical postoperative care. METHODS:This retrospective study included 544 patients with p-stage I LUAD who were randomly allocated to development (272 patients) and validation (272 patients) cohorts. Cox regression and backward model selection were used to develop the prediction model. The predictive performance of the model was then compared with that of the current TNM staging system and two major pathological grading systems. The primary endpoint was RFS. RESULTS:A total of 79 out of 544 patients with p-stage I LUAD experienced recurrence after surgery. Four risk factors were incorporated into a weighted risk index-high-grade patterns ratio, epidermal growth factor receptor mutation status, spread through air spaces status and consolidation tumor ratio-to establish the "CEHS" RFS prediction model. This model demonstrated superior predictive accuracy compared with existing staging and grading systems. High-risk patients had significantly shorter RFS than low-risk patients did. An online algorithm based on the CEHS model was also developed. CONCLUSION:We established and validated a novel model that integrates radiological, molecular and pathological features to predict RFS in patients with p-stage I LUAD. This new model exhibited excellent discriminatory power for classifying early-stage LUAD patients at different risks of recurrence.

ABSTRACT The immune microenvironment of invasive mucinous adenocarcinoma of the lung (IMA), a rare and heterogeneous subtype, remains poorly characterized, limiting insights into its potential response to immunotherapy. In this multicenter study, we systematically evaluated programmed cell death ligand 1 (PD‐L1) expression (using tumor proportion score, TPS, and combined positive score, CPS) and cluster of differentiation 8‐positive (CD8+) tumor‐infiltrating lymphocyte (TIL) infiltration in the largest cohort to date of pathologically confirmed pure IMAs (n = 312), supported by single‑cell transcriptomic analysis. PD‐L1 positivity was low (TPS≥1%: 9.0%; CPS≥1: 28.5%). While PD‐L1 alone showed no prognostic significance, high CD8+ TIL percentage and density were independent, favorable prognostic factors for relapse‐free survival, particularly in patients not receiving adjuvant therapy. By integrating TPS and CD8+ TIL percentage, we established a novel four‐category immune phenotype classification that identified a distinct subgroup (Type IV: PD‐L1+/CD8+) with significantly better outcomes. Preliminary analysis of 20 patients who received immune checkpoint inhibitors suggested that Type IV patients may derive greater clinical benefit. Single‐cell RNA sequencing analyses revealed a paucity of effector CD8+ T cells in IMA. This work defines the unique immune landscape of IMA, introduces a clinically relevant immune phenotyping framework with prognostic and predictive potential, and provides a rationale for future immunotherapeutic strategies in this rare malignancy.

Lung adenocarcinoma (LUAD) presents a paradoxical association between SHOX2 DNA hypermethylation-a well-validated diagnostic biomarker-and its transcriptional overexpression, challenging conventional methylation-cancer biology paradigms. Through validation in our clinical cohort (n = 142) and functional experiments, we demonstrate that SHOX2 overexpression is linked to oncogenic activation, correlates with advanced TNM stage (P = 0.0161), poor tumor differentiation (P = 0.0418), and reduced overall survival (HR = 1.583, 95% CI:1.027-2.442), establishing its role as an independent prognostic factor (multivariate Cox HR = 1.704, P = 0.021). Mechanistically, systematic literature/patent analyses revealed that commercially utilized SHOX2 hypermethylation biomarkers (e.g. Epi proLung BL, LungMe® kits) target CpG sites within the first intron-a gene body region whose methylation enhances oncogenic transcription-rather than promoter regions. Integrative TCGA-LUAD methylation profiling and demethylation experiments (5-aza-dC treatment in H1650/SK-LU-1/H1975/A549/H1299/H322/HCC827/H358 cells) further establish a dual regulatory mechanism: promoter hypomethylation (cg25694447/cg26129769 sites, P < 0.0001) and gene body hypermethylation (cg09220088/cg04521004 sites, P < 0.0001) cooperatively drive SHOX2 overexpression. This spatial resolution explains the high specificity of SHOX2 methylation-based diagnostics despite tumor overexpression, resolving longstanding contradictions. Our findings redefine epigenetic regulation in LUAD, demonstrating that regional methylation patterns-not global promoter status-orchestrate oncogene activation. We propose a novel framework for spatially resolved methylomics, advocating 1) dual-target assays monitoring both promoter and gene body methylation to improve diagnostic precision, and 2) therapeutic exploitation of SHOX2's intronic methylome as a druggable epigenetic switch.

Introduction The optimal neoadjuvant strategy for locally-advanced esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to compare the efficacy and safety of neoadjuvant chemoimmunotherapy (NCIT), chemoradiotherapy (NCRT), and chemotherapy alone (NCT). Methods We retrospectively analyzed perioperative clinical data from ESCC patients treated with NCIT, NCRT, or NCT at the National Cancer Center in China from 2009 to 2023. The primary outcomes were pathological response, survival, recurrence pattern and surgical complications. Results Clinicopathological data from 462 patients (NCIT=122, NCRT=195, NCT=145) were analyzed. The pathological complete response (pCR) rate in the NCIT group (29.5%) was comparable to the NCRT group (28.7%) but significantly higher than the NCT group (3.4%). The overall postoperative complication rate in the NCIT group was higher than in the NCT group (33.6% vs. 14.5%, p<0.001) but comparable to the NCRT group (33.6% vs. 28.2%, p=0.309), with a manageable level. The overall recurrence rates were lower in NCIT (27.0%) than NCRT (48.2%) and NCT (44.1%). Notably, the distant metastasis rate in the NCIT group was significantly lower than that in the NCRT group (11.5% vs. 22.1%, p=0.017) and the NCT group (11.5% vs. 22.8%, p=0.016). As for long-term survival, the 5-year overall survival rate for NCIT was 72.5%, significantly higher than both NCRT (55.7%, p<0.001) and NCT (60.8%, p=0.004). Similarly, the 5-year recurrence-free survival rate for NCIT was 70.7%, significantly surpassing both NCRT (49.8%, p<0.001) and NCT (46.2%, p<0.001). No significant survival differences were observed between the NCRT and NCT groups. Conclusion NCIT provides a significant survival benefit over both NCRT and NCT in locally advanced ESCC in real-world clinical practice, achieving a comparable pCR rate to NCRT and decreased recurrence rate. It’s a favorable neoadjuvant option, with the potential to be a novel treatment strategy. Prospective randomized trials to validate our findings are warranted.

BACKGROUND: Postoperative survival in early-stage lung adenocarcinoma (LUAD) remains heterogeneous. Reliable prognostic biomarkers are needed to refine recurrence-risk stratification and guide individualized care. METHODS: We integrated transcriptomic profiles from 274 stage I LUAD tumors and 637 normal lung tissues across three public datasets—Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO)—to identify differentially expressed genes (DEGs) with functional enrichment analyses. Findings were validated in an independent institutional cohort of 226 resected early-stage LUADs using tissue microarrays (TMAs) and immunohistochemistry (IHC). RESULTS: Nine upregulated genes were associated with improved recurrence-free survival (RFS) including glutathione S-transferase alpha 1 (GSTA1). A three-gene model (NQO1, EPHX1, and GSTA1) stratified patients into high- and low-risk groups. TMA analyses confirmed that higher tumor GSTA1 protein expression correlated with longer RFS. GSTA1 expression was also associated with key clinicopathologic features, including smoking history, presence of ground-glass opacity (GGO), pathological stage, and histologic subtype composition. CONCLUSIONS: High GSTA1 expression is associated with a favorable prognosis in stage I LUAD. Clinically, IHC-based GSTA1 scoring can be integrated into the postoperative workflow as a pragmatic risk-stratification aid: low GSTA1, especially when found alongside adverse features (micropapillary/solid patterns, STAS, or absent GGO), may warrant intensified surveillance and a lower threshold for adjuvant-therapy discussion, whereas high GSTA1 supports standard surveillance in otherwise low-risk profiles.

ABSTRACT Adenosine‐to‐inosine (A‐to‐I) RNA editing, predominantly catalyzed by the enzyme adenosine deaminase acting on RNA 1 (ADAR1), has attracted interest due to its essential functions in regulating immune response and cancer progression. This research investigates ADAR1 inhibition as a promising strategy aimed at improving immunotherapy efficacy in lung adenocarcinoma (LUAD) and explores the underlying mechanisms. Findings from murine models demonstrate that ADAR1 suppression within tumors notably improves the immune microenvironment, marked by increased PD‐L1 expression and enhanced CD8+ T‐cell infiltration, as well as elevated levels of CXCL9, CXCL10, and CXCL11. These changes promote antitumor T‐cell immune responses and amplify the effects of immunotherapy. Mechanistic investigations further reveal that deficiency in ADAR1 leads to an increase in double‐stranded RNA (dsRNA), which serves as a substrate for A‐to‐I editing. This activates downstream signaling via dsRNA receptors, including RIG‐I and MAVS, thereby inducing the IFN‐β pathway. Significantly, IFN‐β contributes to the ADAR1‐dependent modulation of the tumor immune microenvironment and carcinogenesis in LUAD. Clinical validation in LUAD patients further confirms that reduced ADAR1 expression is associated with improved immunotherapy responses. These findings suggest inhibiting ADAR1‐mediated A‐to‐I RNA editing is a promising approach to enhance the efficacy of immunotherapy in LUAD.

BACKGROUND:Neoadjuvant chemoimmunotherapy (NCI) and neoadjuvant targeted therapy (NTT) are cornerstone treatments of locally advanced lung adenocarcinoma (LA). However, their impact on surgical feasibility and long-term survival outcomes remains unclear. METHODS:This dual-center retrospective study included patients with LA who underwent radical surgery after NCI (n = 97) or NTT (n = 105) from January 2020 to December 2022 in the Cancer Hospital Chinese Academy of Medical Sciences and First Affiliated Hospital of China Medical University. Surgical outcomes (minimally invasive surgery rate, conversion to thoracotomy rate, complications), pathologic response of tumor bed and metastatic lymph nodes, and survival outcomes (3-year overall survival and recurrence-free survival) were compared between the groups. RESULTS:Compared with the NCI group, the NTT group had a lower conversion rate (8.6% vs 18.6%; P = .04), reduced postoperative drainage volume (180 mL vs 240 mL; P < .01), and lower incidence of postoperative pneumonia (2.9% vs 10.3%; P = .03). The NCI group demonstrated a higher major pathologic response rate (9.3% vs 1.9%; P = .02). The NTT group achieved superior 3-year recurrence-free survival (73.4% vs 58.6%; P = .03) compared with NCI, with particularly pronounced survival benefits in the gene mutation-positive subgroup (3-year overall survival, 89.5% vs 78.9% [P = .01]; 3-year recurrence-free survival, 72.0% vs 53.7% [P = .02]). CONCLUSIONS:For patients with LA, NTT is associated with reduced surgical complexity, lower conversion rates, and fewer postoperative complications compared with NCI. In addition, NTT is correlated with long-term survival benefits, particularly in patients with gene mutations.

Background:The results of three modern randomized controlled trials have proved sublobar resection as an effective procedure for early-stage non-small cell lung cancer (NSCLC) up to 2 cm. We aimed to examine whether sublobar resection is oncologically feasible and what constitutes adequate lymph node assessment for hypermetabolic clinical stage IA (cIA) NSCLC. Methods:A single-center retrospective study was conducted in 589 patients who underwent lobectomy (n=526) or sublobar resection (n=63) for hypermetabolic cIA NSCLC [maximum standardized uptake value (SUVmax) ≥2.6 g/dL]. The primary outcomes (lung cancer-specific death and tumor recurrence) were compared in a competing risks framework for all patients and the propensity score matched pairs. Random forests were used to examine the variable importance for lung cancer-specific survival and tumor recurrence. Factors affecting pathological upstaging and recurrence-free survival were assessed by logistic regression analysis and Cox regression analysis, respectively. Results:Sublobar resection had significantly higher lung cancer-specific cumulative incidence of death (LC-CID) and cumulative incidence of recurrence (CIR) than lobectomy after matching (5-year LC-CID, 20.8% vs. 6.5%, P<0.001; 5-year CIR, 37.9% vs. 14.8%, P<0.001). Wedge resection was an independent risk factor for both lung-cancer specific death [hazard ratio (HR) =4.17; 95% confidence interval (CI): 2.07-8.36; P<0.001] and recurrence (HR =3.48; 95% CI: 1.91-6.33; P<0.001). Lymphadenectomy that failed to meet the lobe-specific nodal dissection (LSND) criteria correlated with decreased odds of pathological nodal upstaging [odds ratio (OR) =0.55; 95% CI: 0.34-0.87; P=0.01]. While patients with LSND had lower LC-CIR and CIR, there was no additional prognostic benefit of systemic nodal dissection (SND) over LSND. Conclusions:Lobectomy was oncologically superior to sublobar resection as a curative-intent procedure for hypermetabolic cIA NSCLC. Lobectomy plus lobe-specific lymphadenectomy should be considered as the minimum standards of curative resection for hypermetabolic early-stage NSCLC in order to achieve more accurate pathological N staging and better cancer control.

Lead-free halide double perovskite nanocrystals have emerged as one of the most promising alternatives to lead halide perovskite nanocrystals due to their non-toxicity, high stability, and outstanding optoelectronic properties. However, conventional synthesis methods often result in impurities due to increased constituent elements. In this study, an efficient water-oil biphasic interface-driven approach is introduced for synthesizing lead-free double perovskite nanocrystals, enabling controlled structural transformations from 0D to 2D and 3D structures. Starting from 0D Cs3BiBr6, a gradual cation exchange is achieved, forming 3D Cs2AgBiBr6. Real-time monitoring reveals the slow insertion of Ag+ ions as the key to the structural transformation. The resulting Cs2AgBiBr6 nanocrystals exhibit exceptional stability, maintaining their integrity for over 120 days under ambient conditions without significant degradation, showing no considerable material decomposition. Additionally, this method allows for the successful synthesis of 2D layered double perovskite Cs4ZnBi2Br12, which has not previously been reported in experimental studies. This biphasic synthesis strategy provides a universal and reliable method for producing high-quality double perovskite nanocrystals while offering valuable insights into their structural dynamics and properties.

Lung cancer continues to be the primary cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all instances. Recently, immune checkpoint inhibitors (ICIs) have transformed the treatment approach for NSCLC, however, only a subset of patients experiences significant benefits. Therefore, identifying reliable biomarkers to forecast the efficacy of ICIs is crucial for ensuring the safety and effectiveness of treatments, becoming a major focus of current research efforts. This review highlights the recent advances in predictive biomarkers for the efficacy of ICIs in the treatment of NSCLC, including PD-L1 expression, tertiary lymphoid structures (TLS), tumor-infiltrating lymphocytes (TILs), tumor genomic alterations, transcriptional signatures, circulating biomarkers, and the microbiome. Furthermore, it underscores the pivotal roles of liquid biopsy, sequencing technologies, and digital pathology in biomarker discovery. Special attention is given to the predictive value of TLS, circulating biomarkers, and transcriptional signatures. The review concludes that the integration of multiple biomarkers holds promise for achieving more accurate efficacy predictions and optimizing personalized immunotherapy strategies. By providing a comprehensive overview of the current progress, this review offers valuable insights into biomarker-based precision medicine for NSCLC and outlines future research directions.

BACKGROUND:Esophageal cancer (EC) demonstrates poor prognosis and regional disparities. Gastroesophageal reflux disease (GERD) is an established risk factor for adenocarcinoma, though its link to squamous cell carcinoma remains debated. MATERIALS AND METHODS:We analyzed data from 204 countries and territories (1990-2021) using the Global Burden of Disease 2021 study. Incidence and disability-adjusted life years (DALYs) for EC and GERD were assessed by age, sex, and region. Time-series modeling, hierarchical clustering, and time-lagged analysis were employed to explore epidemiological trends and potential associations. RESULTS:In 2021, EC caused 576 529 new cases and 12.99 million DALYs globally, with an age-standardized DALY rate of 148.6 per 100 000. GERD accounted for 324.1 million new cases and 6.34 million DALYs, corresponding to a rate of 75.6 per 100 000. East Asia had the highest EC burden, while GERD burden peaked in Tropical Latin America. From 1990 to 2021, EC burden declined, while GERD increased slightly. EC burden remained high in men and in high-middle sociodemographic index (SDI) regions. GERD showed less sex disparity and was highest in low-middle SDI regions. Major regional risk factors included smoking (East Asia), alcohol (Europe), and tobacco chewing (South Asia). Forecasts suggested rising GERD burden and fluctuating EC trends. No global causal link was found between GERD and EC, but region- and sex-specific associations were observed, notably in Central Sub-Saharan Africa and among Australasian females. CONCLUSION:Despite declining trends of EC burden, geographical and demographic disparities persist. Rising GERD prevalence may affect future EC risk in some populations. Region-specific prevention strategies targeting GERD and known EC risk factors are warranted.

ObjectiveThe purpose of this study was to evaluate the predictive values of systemic immune-inflammatory index (SII), prognostic nutrition index (PNI), change of SII (ΔSII), change of PNI (ΔPNI) and ΔPNI-ΔSII score in patients with neoadjuvant chemotherapy for breast cancer.MethodsWe enrolled in a retrospective study involving 72 patients with breast cancer between February 2020 and January 2022. All patients had clinical features of axillary lymph node metastasis and received neoadjuvant therapy. PNI and SII were detected by hematology before and after treatment. Chi-square test was used to compare the clinicopathological and experimental parameters among all groups. Logistic regression analysis was used to evaluate the prognostic value of each factor.ResultsThe prognosis was evaluated and 18 patients (25%) achieved pathological complete response (pCR) after neoadjuvant therapy. The pCR rate of breast cancer patients was significantly correlated with ER, PR, HER-2, molecular subsets, tumor size, vascular invasion, nerve invasion, N stage, clinical stage and chemotherapy regimen. Low ΔPNI, high ΔSII and higher ΔPNI-ΔSII score values had better prediction of therapeutic effect, especially the ΔPNI-ΔSII score.ConclusionIn breast cancer patients receiving neoadjuvant chemotherapy, ΔPNI-ΔSII score is an effective predictor of efficacy, which helps to identify high-risk groups and evaluate efficacy.

BACKGROUND:Neoadjuvant camrelizumab plus apatinib has shown a promising major pathological response (primary endpoint) and pathological complete response (a secondary endpoint) in patients with resectable stage IIA-IIIB non-small-cell lung cancer (NSCLC) in a previous single-arm phase 2 trial. Here, we present the 3-year survival outcomes and potential prognostic factors with extended follow-up. METHODS:This single-arm phase 2 study enrolled patients with resectable stage IIA-IIIB NSCLC (stage IIIB, T3N2 only, according to the eighth edition of the American Joint Commission on Cancer TNM staging classification). Patients received three cycles of neoadjuvant camrelizumab (200 mg, intravenously, q2w) and apatinib (250 mg, orally, qd, for 5 days followed by 2 days off) followed by surgery. At 4-8 weeks after surgery, patients received either adjuvant camrelizumab monotherapy for up to 12 cycles or other strategies at the investigator's discretion. RESULTS:With the median follow-up of 42.6 months, the 3-year event-free survival (EFS), disease-free survival and overall survival were 58.9 % (95 % CI 46.9-69.1), 61.5 % (95 % CI 48.6-72.1), and 92.3 % (95 % CI 83.6-96.5), respectively. Among the pathological responses, residual viable tumors of ≤ 20 % were more strongly associated with improved EFS (HR 0.30, 95 % CI 0.13-0.72). Additionally, metabolic response on PET/CT after neoadjuvant treatment and ctDNA clearance during the perioperative period were significantly associated with improved EFS (HR 0.23 [95 % CI 0.08-0.62] and HR 0.23 [95 % CI 0.09-0.59], respectively). CONCLUSIONS:Neoadjuvant camrelizumab plus apatinib provides a potential sustained benefit for patients with resectable stage IIA-IIIB NSCLC. Metabolic response on PET/CT and perioperative ctDNA clearance might be potential biomarkers for predicting survival.

Increased public health awareness and expanded low-dose computed tomography (CT) utilization, accelerated by the COVID-19 pandemic, have elevated detection rates of pulmonary ground-glass nodules (GGNs). Patients with multiple primary lung cancer (MPLC) often present with multiple GGNs, posing challenges for precise treatment and prognostic assessment. Current therapies including stereotactic body radiation therapy (SBRT), chemotherapy, and immunotherapy face efficacy and safety limitations. While video-assisted thoracic surgery (VATS) is the primary treatment for high-risk GGNs, the sole reliance on surgery may cause excessive loss of lung function. Image-guided thermal ablation techniques can effectively treat smaller lesions with lung preservation. This review explores molecular mechanisms of ablation, VATS-ablation synergy, and the potential value of this approach in combination with immunotherapy. The clinical application prospects, including advancements in navigation techniques and equipment, are also discussed. Overall, this hybrid surgical strategy represents a promising option for patients with multiple lesions, minimizing lung function loss and the psychological burden.

Pyroptosis has emerged as a promising approach for cancer immunotherapy. However, current pyroptosis inducers lack specificity for cancer cells and have a weak antitumour immune response. Here we report a tumour-specific nanoparticle (NP-NH-D5) that activates pyroptosis by disrupting lysosomes for cancer immunotherapy. NP-NH-D5 undergoes negative-to-positive charge reversal and nanoparticle-to-nanofibre transformation within tumour cell lysosomes through tandem response to extracellular matrix metallopeptidase-2 and intracellular reducing agents. The as-formed non-peptide nanofibres efficiently break the lysosomes and trigger gasdermin-D-mediated pyroptosis, leading to strong immunogenic cell death and alleviation of the immunosuppressive tumour microenvironment. In vivo, NP-NH-D5 inhibits orthotopic 4T1 breast tumours, prevents metastasis and recurrence, and prolongs survival without systemic side effects. Furthermore, it greatly enhances the effectiveness of PD-L1 antibody immunotherapy in the 4T1 late-stage lung metastasis and aggressive orthotopic Pan02 pancreatic tumour models. Our research may open pathways for developing stimuli-responsive pyroptosis inducers for precise cancer immunotherapy.

BACKGROUND:Recently, the incidence of multiple pulmonary nodules (MPNs) is gradually rising. Therefore, this study aims to evaluate the safety and efficacy of computed tomography (CT)-guided radiofrequency ablation (RFA) combined with video-assisted thoracoscopic surgery (VATS) for patients with MPNs. MATERIAL AND METHODS:The clinicopathological data and perioperative results of the patients with MPNs who underwent RFA combined with VATS at our center from October 2022 to September 2024 were reviewed. The primary endpoints were the safety and feasibility of this combined technique. RESULTS:A total of 105 patients were enrolled in this study, including 30 males and 75 females with a mean age of 55.1 years. In total, 293 lesions were treated, 113 of which were ablated and 180 were surgically resected. The mean nodule size was 6.58 mm for ablated nodules and 10.3 mm for resected nodules. Of the 113 nodules treated using RFA, 112 were ground-glass nodules. The median ablation time and power of RFA were 5 min and 60 W, respectively. Of the 180 surgically resected nodules, 169 had ground-glass opacity. Total postoperative complication morbidity was 9.5% (10/105), with major complications (Clavien-Dindo classification ≥ 3) in 1.0% (1/105). No perioperative deaths occurred, and the median hospital stay was 5 days (range, 5-7 days). Notably, no recurrence has been observed in any patients during the short-term follow-up period. CONCLUSIONS:Our study demonstrated that CT-guided RFA combined with VATS is a safe and feasible therapeutic technique for the patients with MPNs. Given the increasing incidence of MPNs, this combination strategy holds significant potential for clinical application.

BACKGROUND:With the advancement of diagnostic technology and changes in living environment, the incidence of synchronous multiple primary lung cancer (sMPLC) is increasing. This study aims to investigate the impact of surgical timing on clinical outcomes. METHODS:This multi-institutional cohort study retrospectively enrolled 901 patients with bilateral sMPLC who underwent two surgeries from January 2017 to December 2022. Three different subgroups were determined based on the time interval between the 1st surgery and the 2nd surgery: Group-I (time interval ≤ 90 days), Group-II (90 days < time interval ≤ 180 days) and Group-III (time interval > 180 days). RESULTS:For the entire cohort, the median follow-up time from the second surgery was 49.2 months. The clinical outcomes of patients in Group-II were more favourable than those in Group-I and Group-III (log-rank, OS, p = 0.0037; DFS, p < 0.0001). According to multivariable Cox regression analyses, patients in Group-I (HR, 1.704; 95% CI, 0.828-3.51; p = 0.148) and Group-III (HR, 5.369; 95% CI, 2.664-10.819; p < 0.001) may be associated with poor prognosis compared with those in Group-II. In addition, patients in Group-III had a high incidence of postoperative complications, and significantly reduced lung function was identified among patients in Group-I. CONCLUSIONS:For patients with bilateral sMPLC, our research identified a potential correlation between the interval of subsequent surgeries and patient prognosis. We suggest that an interval of 90 to 180 days between surgeries may be the most beneficial.