BackgroundBefore surgical resection of lung tumor, intraoperative biopsy is needed for cancer diagnosis, while current techniques that guide biopsy have limited performance in tumor identification and boundary determination. Remodeling of extracellular matrix (ECM), mainly collagen and elastin fibers, is an emerging hallmark of tumorigenesis.MethodsHerein, we establish a quantitative multiphoton microscopy (MPM) imaging method for time-efficient, highly-sensitive lung cancer detection via characterization of ECM remodeling. From label-free images of collagen and elastin fibers acquired simultaneously, we construct a similarity coefficient (SC) metric to describe their interaction, and further develop an artificial intelligence (AI)-ECM framework by producing a fiber voxel dictionary via unsupervised learning of morpho-structural features for explainable and visible assessments of cancer risk.ResultsThe application is demonstrated by ex vivo human lung cancer diagnosis with a sensitivity of 99.37%, and recognizing the tumor boundary. The translational potential is further revealed via in vivo imaging of a murine model harboring human lung cancer.ConclusionsThis technology can help surgeons perform more precise biopsies and surgeries by providing explainable visual cues, thus leading to better outcomes for lung cancer patients.

Lung cancer leads to a series of physiological abnormalities. The remodeling of extracellular matrix (especially elastin and collagen fibers) has been drawing increasing attention as it is suggested to be a hallmark of tumorigenesis. However, the interaction between these crucial matrix components, together with their relationship to mechanical changes, remains poorly understood. Here, we develop a quantitative multiphoton microscopy system to elucidate the relationship between tissue stiffening and elastin-collagen interplay in lung cancer. Based on label-free images of both fibers, we establish a metric termed resemblance metric (RM) to characterize their interaction by quantifying the similarity of their morpho-structural distributions. Specifically, RM is found to increase with lung tumorigenesis, and exhibits superior sensitivity in identifying human lung cancer through ex vivo quantitative imaging. Nanoindentation results suggest a strong correlation between tissue stiffness and inter-channel interaction, notably greater than that between stiffness and any individual morpho-structural feature of either fiber type. Finally, the translational potential of RM-based imaging is demonstrated through tumor boundary identification via in vivo imaging within a mouse model harboring human lung cancer.

Objective: To assess the efficacy of this approach and establish the criteria that identify patients with locally advanced pancreatic cancer (LAPC) who may achieve survival benefits from radical resection combined with intestinal autotransplantation (RRCIA).Background: Surgical resection for LAPC remains challenging and is associated with high morbidity and mortality, especially for surgery with major arterial reconstruction. We previously showed the feasibility and safety of RRCIA after systemic treatment.Methods: A retrospectively observational and prospectively validated study with 3 cohorts was conducted using multiple treatments. Overall survival (OS) and progression-free survival (PFS) were compared for both analyses. Propensity-score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) were performed to adjust for potential confounders.Results: Among 208 patients with LAPC, we identified 48 who underwent systemic treatment followed by RRCIA. Using PSM and stabilized IPTW analyses, we observed that patients who underwent RRCIA had better overall and PFS compared with patients who did not have surgery (PSM cohort: median OS: 25.8 vs 14.2 months, P = 0.0031, and IPTW cohort: median OS: 23.2 vs 15.4 months, P = 0.0069) and PFS (PSM cohort: median PFS: 13.3 vs 7.0 months, P = 0.0246, and IPTW cohort: median OS: 13.3 vs 8.8 months, P = 0.002). Further prospective analysis showed that patients who received systemic treatment, followed by RRCIA, were associated with improved OS and PFS compared with patients who were eligible but did not receive RRCIA (median OS: 22.6 vs 18.2 months, P = 0.035; median PFS: 13.2 vs 10.3 months, P = 0.0412). Moreover, the stratified and multivariable analysis demonstrated that preoperative carbohydrate antigen 19-9 normalization and duration of initial treatment over 8 cycles were predictors for the precise selection of patients who would benefit from RRCIA. Meanwhile, adjuvant therapy after RRCIA was a significant factor in improving survival.Conclusions: This study suggests that RRCIA appears to be effective and associated with improved outcomes for patients with LAPC with favorable responses to systemic treatment. Patients with LAPC Should have at least 8 cycles of systemic treatment and carbohydrate antigen 19-9 normalization to be considered for RRCIA.

Glypican-3 (GPC3) is highly expressed in hepatocellular carcinoma (HCC), making it an attractive target for chimeric antigen receptor (CAR) T cell therapy; however, this approach has previously shown limited clinical efficacy, potentially owing to high levels of transforming growth factor-β (TGFβ) in the tumour microenvironment1-4. We therefore engineered CAR T cells with a dominant-negative TGFβ receptor II, which showed enhanced antitumour activity in preclinical studies5. Here we report findings from a first-in-human trial evaluating the safety and efficacy of C-CAR031 in patients with advanced, treatment-refractory HCC ( NCT05155189 ). Thirty-six patients received CAR T infusions at four dose levels (from 0.75 × 106 to 4.0 × 106 cells per kg). Cytokine release syndrome was reported in 34 patients, of which two cases were grade 3. Nine patients had non-haematological adverse events of grade 3 or higher. Tumour regression was observed in 32 patients, with a median best tumour reduction from baseline of 41.6% (range: 3.4-94.4%) in target lesions. The objective response rate was 44.4%, and the median duration of response was 4.4 months (95% confidence interval: 2.9-7.4). Median progression-free survival and overall survival were 4.2 months (95% confidence interval: 2.9-4.8) and 14.2 months (95% confidence interval: 10.1 to not evaluable), respectively. High-throughput analyses of tumour samples and functional validation suggested that GPC3 antigen loss and increased TGFβ levels may contribute to C-CAR031 resistance. Collectively, these results indicate that C-CAR031 has a manageable safety profile and encouraging antitumour activity in heavily pretreated patients with advanced HCC.

Ovarian cancer (OC) has a dismal prognosis due to late diagnosis and platinum resistance, with the molecular mechanisms linking cuproptosis, lncRNAs, and the tumor microenvironment (TME) remaining poorly defined. LncRNA ENSG00000253374 was previously identified as a prognostic biomarker for OC, while its correlation with cuproptosis and platinum resistance remains unclear. Integrated bulk RNA-seq (TCGA-OV) and single-cell RNA-seq (GSE300897) analyses were performed, combined with in vitro CCK-8 assays, intracellular Cu⁺ detection, survival analysis, WGCNA, pseudotime trajectory, CellChat, virtual knockout, and functional enrichment analyses. OC cells with ENSG00000253374 knockdown were subjected to cuproptosis induction, and GLS-centered co-expression patterns and TME features were characterized. ENSG00000253374 knockdown correlates with altered cellular response to cuproptosis induction, and shows close expression correlation with GLS. The ENSG00000253374–GLS correlated signature is linked to abnormal glutamine metabolism, cell cycle and stemness features, and is associated with immunosuppressive myeloid differentiation and enhanced pro-resistance intercellular communication that correlate with platinum refractoriness. WGCNA constructed a GLS-centered co-expression network enriched in immune and stromal remodeling pathways; in silico GLS perturbation predicted altered stemness, angiogenesis and apoptotic signaling signatures. Elevated GLS expression in tumor and stromal cells coincides with stronger TME crosstalk and dominant M2 macrophage populations. LncRNA transcripts of the ENSG00000253374 locus are associated with platinum-resistant ovarian cancer phenotypes via a GLS-related correlative signature, alongside disrupted cuproptosis and metabolic-immune remodeling. Our in vitro assays reflect overall transcriptional activity of this genomic locus rather than single splice variant function. ENSG00000253374 and GLS may serve as candidate prognostic biomarkers. Combinatorial interventions targeting this correlative axis together with cuproptosis inducers or immune modulators could provide potential strategies to relieve platinum resistance in OC.

This study aimed to explore the diagnostic value of Gd-EOB-DTPA enhanced MRI in hepatocellular carcinoma (HCC) with hyperintensity on hepatobiliary phase (HBP) under the background of cirrhosis. A retrospective analysis was conducted on 130 patients diagnosed with cirrhosis and exhibiting hyperintense lesions on HBP in Gd-EOB-DTPA enhanced MRI from January 2015 to December 2022. Of these patients, 56 were diagnosed with hepatocellular carcinoma and 74 had benign cirrhotic nodules. The morphology, signal characteristics, diameter, and ADC value of each lesion were evaluated. Univariate analysis and multivariate logistic regression analysis were performed to determine the independent risk factors of hepatocellular carcinoma and construct a diagnostic model. The diagnostic performance of the model was evaluated using a receiver operating characteristic (ROC) curve. We established a diagnostic model by combining the independent risk factors of HCC with hyperintensity on HBP, with an area under the ROC curve of 0.953, sensitivity and specificity were 92.86

Background and Aims:The role of adjuvant transarterial chemoembolization (TACE) for HCC following curative resection remains controversial. We aimed to determine the effectiveness of postoperative adjuvant TACE in patients with HCC.Approach and Results:In this randomized phase 3 trial, histologically confirmed patients with HCC (American Joint Committee on Cancer TNM stage I and II) were randomly assigned (1:1) to adjuvant TACE or observation groups. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat (ITT) population. The secondary endpoints included overall survival and safety. A total of 332 patients (ITT population) were randomly assigned to the TACE group (n=166) or the observation group (n=166) between March 2014 and June 2021. The RFS was comparable between the 2 groups from the ITT population (median, both unreached; HR, 0.88; 95% CI: 0.62-1.24; p=0.468). The RFS rates at 1, 3, and 5 years were 87.3% (95% CI: 81.2-91.5), 70.7% (95% CI: 63.0-77.0), and 60.6% (95% CI: 51.9-68.3) in the adjuvant TACE group and 84.8% (95% CI: 78.3-89.5), 69.3% (95% CI: 61.6-75.8), and 58.1% (95% CI: 49.5-65.8) in the observation group, respectively. The overall survival was comparable between the TACE group and the observation group in the ITT population (median, both unreached, HR, 1.06; 95% CI: 0.63-1.76; p=0.838). There was no grade >= 3 adverse event or treatment-related death in either group.Conclusions:Postoperative adjuvant TACE was not associated with prolonged RFS or overall survival in patients with American Joint Committee on Cancer TNM stage I or II HCC.

This single-center, randomized phase 3 trial (NCT03750669) evaluated sequential neoadjuvant nab-paclitaxel plus gemcitabine followed by modified FOLFIRINOX versus upfront surgery in 324 patients with resectable pancreatic cancer. Patients in the neoadjuvant group received nab-paclitaxel plus gemcitabine followed by modified FOLFIRINOX before surgery and then four cycles of adjuvant therapy (preferably gemcitabine plus capecitabine), while those in the upfront surgery group underwent immediate resection followed by six cycles of adjuvant therapy. The primary endpoint was event-free survival. Notably, 50% of patients had tumors in the pancreatic body or tail. Median event-free survival was 15.3 months (95% confidence interval [CI], 12.6-19.3) versus 10.9 months (95% CI, 9.1-13.5; hazard ratio [HR], 0.71; 95% CI, 0.54-0.93; p = 0.0136). Median overall survival was 35.4 months versus 27.2 months (HR, 0.73; 95% CI, 0.53-1.00; nominal p = 0.0477). Grade ≥3 adverse events occurred in 47.6% versus 30.7% of patients. This neoadjuvant regimen improves event-free survival with manageable safety.

Most cervical cancers develop from squamous cells in the exocervix followed by stromal invasion, which alters the organization and morphology of collagen fibers. Therefore, morpho-structural remodeling of collagen fibers is closely associated with cancer progression. Collagen-based cancer detection requires not only techniques capable of qualified large-depth imaging but also computational sensitivity to extract subtle changes. Here, optical coherence tomography (OCT) is applied to collagen fibers in the exocervix. High-quality imaging into deep stroma is guaranteed by an all-fiber probe designed to have an extended depth of focus through the formation of the quasi-Bessel focusing beam. Collagen fibers provide dominant scattering signals in OCT images, and volume information is utilized to establish an optical biomarker reflecting variation gradient in fiber alignment and crimping. Detection of cervical cancer with a multi-parametric method is then evaluated by ex vivo imaging of human specimens and in vivo imaging of a murine model harboring human cervical cancer. Finally, the tumor potential index (TPI) is proposed by merging multiple metrics. The TPI map provides an intuitive illustration of cancer risk, which may guide clinicians more accurately to the correct location for biopsy.

BACKGROUND:No consistent clinical criteria and multimodal approaches to manage liver metastatic pancreatic cancer patients after effective systemic treatment have been developed. This study aims to assess the efficacy of surgical resection, liver-directed local therapy, or continuous systemic treatment in liver metastatic pancreatic cancer patients with favorable systemic treatment response. MATERIALS AND METHODS:It was a retrospective observational study on 360 patients with liver metastatic pancreatic cancer. Patients were divided into four groups according to the treatment methods they received: surgery with/without liver-directed local therapy; non-surgery with/without liver-directed local therapy. Their overall survival (OS) and progression-free survival (PFS) were compared. RESULTS:Forty-eight patients underwent surgery after systemic treatment. Patients who underwent surgery with liver-directed local therapy had superior outcomes than those who had only surgery without liver-directed local therapy (median OS: 47.2 vs. 18.3 months, P = 0.035; median PFS: 28.5 vs. 12.1 months, P = 0.017) and nonsurgical treatment (median OS: 47.2 vs. 19.1 months, P = 0.001; median PFS: 28.5 vs. 10.2 months, P = 0.002). Patients who underwent surgery without liver-directed local therapy had a similar prognosis as those with nonsurgical treatment. The OS of the non-surgery with liver-directed local therapy group was not significantly different from that of the non-surgery without liver-directed local therapy group (median OS: 19.0 vs. 11.5 months, P = 0.302). However, the PFS of the former was significantly superior to that of the latter (median PFS: 13.9 vs. 8.2 months, P = 0.037). CONCLUSION:Surgical resection with liver-directed local therapy is the best approach to improve outcomes for liver metastatic pancreatic cancer patients after systemic treatment. Resection of the primary tumor or liver-directed local therapy alone, compared to continuous systemic treatment, failed to extend liver metastatic pancreatic cancer patient survival.

Metabolic reprogramming shapes the tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of protumor macrophages, and reduced cytotoxic T cells in the TME. Analysis of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in patients showed that increased global protein lactylation in PDAC correlates with worse clinical outcomes in immunotherapy. Inhibition of lactate production in pancreatic tumors via glycolysis or mutant-KRAS inhibition reshaped the TME, thereby increasing their sensitivity to immune checkpoint blockade (ICB) therapy. In pancreatic tumor cells, lactate induces K63 lactylation of endosulfine α (ENSA-K63la), a crucial step that triggers STAT3/CCL2 signaling. Consequently, elevated CCL2 secreted by tumor cells facilitates tumor-associated macrophage (TAM) recruitment to the TME. High levels of lactate also drive transcriptional reprogramming in TAMs via ENSA-STAT3 signaling, promoting an immunosuppressive environment. Targeting ENSA-K63la or CCL2 enhances the efficacy of ICB therapy in murine and humanized pancreatic tumor models. In conclusion, elevated lactylation reshapes the TME and promotes immunotherapy resistance in PDAC. A therapeutic approach targeting ENSA-K63la or CCL2 has shown promise in sensitizing pancreatic cancer immunotherapy.

ABSTRACT Introduction Standard treatments provide limited benefits for patients with intermediate‐ or advanced‐stage hepatocellular carcinoma (HCC). This retrospective observational study aimed to assess the potential improvements in outcomes associated with systemic therapies in patients receiving transarterial chemoembolization (TACE) for initially unresectable HCC. Methods Between February 2019 and March 2023, we reviewed patients diagnosed with intermediate‐to‐advanced HCC who were treated with either TACE or TACE combined with antiangiogenic agents and immune checkpoint inhibitors (combination therapy) as their initial treatment. To address potential confounding biases, patients were further stratified into surgical and non‐surgical cohorts, and separate analyses were conducted. The primary endpoints were progression‐free survival (PFS) and overall survival (OS), with safety profiles also evaluated. Results Among 279 patients with initially unresectable intermediate or advanced HCC, 156 successfully underwent curative‐intent liver resection after preoperative treatments (TACE group, n = 69; combination group, n = 87), while 123 patients continued with non‐surgical treatments (TACE group, n = 31; combination group, n = 92). After propensity score matching, 26 matched patient pairs were generated within the non‐surgical cohort. The combination group exhibited significantly improved PFS in non‐surgical patients compared with the TACE group (9.4 vs. 7.2 months, p = 0.043). Cox proportional hazards analysis further confirmed that combination therapy was associated with improved PFS (hazard ratio = 0.476, 95% confidence interval: 0.257–0.883, p = 0.019). For surgical patients exceeding the up‐to‐seven criteria, the combination group demonstrated superior median PFS (18.0 vs. 14.6 months, p = 0.03) and OS (not reached vs. 50.1 months, p = 0.049) compared with the TACE group. Adverse events were manageable, with no treatment‐related fatalities reported. Conclusion Combination therapy with TACE demonstrated enhanced survival benefits for patients with intermediate to advanced HCC, particularly in surgical patients with higher tumor burdens.

Tumor micronecrosis is a validated malignancy biomarker with poor prognosis in hepatocellular carcinoma (HCC), but currently lacks reliable preoperative detection methods. We developed a radiomics model for predicting tumor micronecrosis using preoperative contrast-enhanced computed tomography (CECT). The study included 1017 patients with histopathologically confirmed HCC across three centers, allocated to development, internal test, external test, and application sets. Radiomics features were extracted from tumor regions, with model training via a stratified 5-fold cross-validation framework. The model yield area under the curve values of 0.80 and 0.75 in the internal and external test sets, respectively. Survival curves for histologic and radiomics-predicted micronecrosis groups demonstrated close alignment. For patients treated with tyrosine kinase inhibitor and anti-PD-(L)1 immunotherapy, radiomics-predicted micronecrosis(−) and micronecrosis(+) groups showed comparable survival (P = 0.312). Mass cytometry demonstrated significant correlations between micronecrosis-associated radiomics features and peripheral CD24+ B cells and neutrophils. The radiomics model shows promise for preoperative micronecrosis assessment.

e16299 Background: Biliary tract malignancies are often diagnosed at advanced stages and carry a poor prognosis. While surgical resection remains the only potentially curative option, few patients are eligible at diagnosis, and recurrence rates are high even after achieving R0 resection. Preclinical and early clinical evidence suggests that combining immune checkpoint inhibitors, antiangiogenic agents, and chemotherapy may enhance tumor shrinkage and improve R0 resection rates. This multicenter phase II trial evaluates the efficacy and safety of perioperative camrelizumab plus apatinib and gemcitabine-oxaliplatin (GEMOX) in patients with borderline resectable biliary tract malignancies. Methods: Patients aged 18-75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, pathologically confirmed biliary tract cancers, and borderline resectable disease (stage II-IIIC) were enrolled between November 2022 and December 2024. Participants received camrelizumab (200 mg every 3 weeks) and apatinib (250 mg daily) combined with gemcitabine (800 mg/m² on days 1 and 8) and oxaliplatin (85 mg/m² on day 1) for two cycles. Surgical resectability was assessed, and patients underwent surgery if feasible; otherwise, up to two additional cycles could be administered. Postoperatively, camrelizumab and S-1 were continued for up to 6 months or until disease progression or unacceptable toxicity. The primary endpoint was 1-year event-free survival (EFS) rate. Secondary endpoints included objective response rate (ORR), R0 resection rate, disease control rate (DCR), and safety. Results: Among 28 enrolled patients, the median age was 64.5 years (range: 50-75), with a male-to-female ratio of 12:16. ECOG performance status was 0 in 3 patients and 1 in 25. Cholangiocarcinoma was diagnosed in 25 patients (16 intrahepatic, 8 perihilar, 1 distal) and gallbladder carcinoma in 3. Initial staging included stage II (n = 3), IIIA (n = 4), IIIB (n = 16), and IIIC (n = 5). The ORR was 64.3% (18/28), and the DCR was 96.4% (27/28). Surgery was performed in 57.1% (16/28) of patients, and R0 resection was achieved in 87.5% (14/16). The 1-year EFS data remain immature. Grade ≥3 hematologic toxicities included neutropenia (28.6%), thrombocytopenia (14.3%), and anemia (10.7%). Grade ≥3 non-hematologic toxicities included elevated aspartate aminotransferase (14.2%), proteinuria (10.8%), and elevated thyroid-stimulating hormone (3.6%). Conclusions: Perioperative camrelizumab plus apatinib and GEMOX demonstrated high ORR and R0 resection rates in patients with borderline resectable biliary tract malignancies. Toxicities were manageable and consistent with the known safety profiles of these agents. These findings warrant further exploration of this regimen as a potentially effective multimodal treatment strategy. Clinical trial information: NCT05451290 .

OBJECTIVE:To assess the efficacy of this approach and establish the criteria that identify patients with locally advanced pancreatic cancer (LAPC) who may achieve survival benefits from radical resection combined with intestinal autotransplantation (RRCIA). BACKGROUND:Surgical resection for LAPC remains challenging and is associated with high morbidity and mortality, especially for surgery with major arterial reconstruction. We previously showed the feasibility and safety of RRCIA after systemic treatment. METHODS:A retrospectively observational and prospectively validated study with 3 cohorts was conducted using multiple treatments. Overall survival (OS) and progression-free survival (PFS) were compared for both analyses. Propensity-score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) were performed to adjust for potential confounders. RESULTS:Among 208 patients with LAPC, we identified 48 who underwent systemic treatment followed by RRCIA. Using PSM and stabilized IPTW analyses, we observed that patients who underwent RRCIA had better overall and PFS compared with patients who did not have surgery (PSM cohort: median OS: 25.8 vs 14.2 months, P = 0.0031, and IPTW cohort: median OS: 23.2 vs 15.4 months, P = 0.0069) and PFS (PSM cohort: median PFS: 13.3 vs 7.0 months, P = 0.0246, and IPTW cohort: median OS: 13.3 vs 8.8 months, P = 0.002). Further prospective analysis showed that patients who received systemic treatment, followed by RRCIA, were associated with improved OS and PFS compared with patients who were eligible but did not receive RRCIA (median OS: 22.6 vs 18.2 months, P = 0.035; median PFS: 13.2 vs 10.3 months, P = 0.0412). Moreover, the stratified and multivariable analysis demonstrated that preoperative carbohydrate antigen 19-9 normalization and duration of initial treatment over 8 cycles were predictors for the precise selection of patients who would benefit from RRCIA. Meanwhile, adjuvant therapy after RRCIA was a significant factor in improving survival. CONCLUSIONS:This study suggests that RRCIA appears to be effective and associated with improved outcomes for patients with LAPC with favorable responses to systemic treatment. Patients with LAPC Should have at least 8 cycles of systemic treatment and carbohydrate antigen 19-9 normalization to be considered for RRCIA.

Background Pelvic organ prolapse (POP), characterised by the downward displacement of pelvic organs, is a prevalent disorder that affects adult women. This study explored the therapeutic potential of PX-478, a selective hypoxia-inducible factor-1α (HIF-1α) inhibitor, in a murine POP model.Methods A murine POP model was established through ovariectomy, mimicking oestrogen deprivation. Fifteen C57BL/6J mice were randomly assigned to control, POP, and PX-478 groups. PX-478, targeting HIF-1α, was administered intravaginally. The analysis of fibroblasts, macrophage and inflammation was performed through Masson staining, immunofluorescence, and ELISA. Collagen distribution was assessed using Sirius Red staining. Expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP-1) were determined through immunohistochemistry and western blot. Fibroblast proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry.Results PX-478 treatment significantly reduced vaginal length, indicating a therapeutic effect on POP severity. Masson staining revealed reduced fibrotic changes and collagen disruption in PX-478-treated mice. Immunofluorescence showed increased fibroblast markers (Vimentin, α-SMA) and collagen fibres by PX-478. Sirius Red staining indicated PX-478 mitigated damage to Type I and Type III collagen fibres. PX-478 significantly reduced MMP-2 and MMP-9 expression while increased TIMP-1. In macrophages, PX-478 decreased M1 and M2 markers (CD80, CD206) and IL-18 secretion. Fibroblasts exhibited increased proliferation, reduced apoptosis, and altered MMP/TIMP expression under PX-478 influence.Conclusion PX-478 demonstrates a therapeutic potential in the mice POP model. It reduces vaginal length, attenuates fibrosis, and modulates collagen synthesis. Its immunomodulation is evident through reduced M1 and M2 macrophages and suppressed IL-18 secretion.

Background: An extensive body of research has explored the role of autophagy in hepatocellular carcinoma (HCC), revealing its critical involvement in the disease’s pathogenesis, progression, and therapeutic targeting. However, there is a discernible deficit in quantitative, analytical studies concerning autophagy in the context of HCC. Accordingly, this investigation endeavored to meticulously assess the evolution of autophagy research, employing bibliometric citation analysis to offer a comprehensive evaluation of the findings in this field. Methods: We conducted a literature search on August 2, 2023, to extract relevant publications spanning from 2013 to 2022, indexed in the Science Citation Index-Expanded (SCIE) of the Web of Science Core Collection (WOSCC). Subsequently, we performed a bibliometric assessment of the compiled documents using visualization tools such as CiteSpace and VOSviewer. Results: The search yielded 734 publications penned by 4,699 authors, encompassing contributions from 41 countries and 909 institutions, disseminated across 272 journals, and comprising 26,295 co-cited references from 2,667 journals. Notably, China led in publication volume with 264 articles (amounting to 35.9%) and exhibited the most robust collaboration with the United States. The mechanisms underlying autophagy’s influence on the emergence and advancement of HCC, as well as the implicated proteins and genes, have garnered significant attention. In recent years, investigations of targeting autophagy and the resistance to sorafenib have surfaced as pivotal themes and emerging frontiers in this domain. Conclusion: This study rigorously collated and distilled the prevailing research narratives and novel insights on autophagy in HCC. The resultant synthesis provides a substantive foundation for medical professionals and researchers, as well as pivotal implications for future investigative endeavors in this arena.

aDepartment of Hepatobiliary Surgery bDepartment of Oncology, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Hepatobiliary Surgery, Chengdu Second People's Hospital, No. 10 Qingyun South Street, Chengdu 610021, People's Republic of China. Tel.: +86 15184302720. E-mail: [email protected] (T. He). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

Background: As a systemic disease, pancreatic cancer (PC) can be treated systemically to raise the R0 resection rate and enhance patient prognosis. The best ways to assess the treatment response to systemic treatment of patients with PC are still lacking. Methods: A total of 122 PC patients were enrolled; 25 of these patients were used as an independent testing set. According to the pathologic response, PC patients were classified into the responder and nonresponder groups. The whole tumor, core, edge, and peritumoral were segmented from the enhanced computed tomography (CT) images. Machine-learning models were created by extracting the variations in radionics features before and after therapy (delta radiomics features). Finally, we compared the performance of models based on radiomics features, changes in tumor markers, and radiologic evaluation. Results: The model based on the core (area under curve [AUC] = 0.864) and edge features (AUC = 0.853) showed better performance than that based on the whole tumor (AUC = 0.847) or peritumoral area (AUC = 0.846). Moreover, the tumor core_edge combination model (AUC = 0.899) could better increase confidence in treatment response than using either of them alone. The accuracies of models based on changes in tumor markers and radiologic evaluation were relatively poorer than of the radiomics model. Moreover, Patients predicted to respond to therapy using the radiomics model showed a relatively longer overall survival (43 vs 27 months), although there were no significant differences (P = .063). Conclusions: The tumor core_edge combination delta radiomics model is an effective approach to evaluate pathologic response in PC patients with systemic treatment.