Background and purposePredicting overall survival (OS) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC) treated with immune checkpoint inhibitors remains challenging due to heterogeneous clinical response. Furthermore, the application of advanced deep learning is hindered by limited immunotherapy datasets. This study aimed to develop a novel prognostic framework by integrating voxel-level deep radiomics derived from pretreatment imaging with a knowledge transfer strategy to accurately predict OS.Materials and methodsA total of 526 patients were respectively identified. A non-immunotherapy dataset from the RTOG 0617 clinical trial was used to pre-train a Vision-Mamba deep learning model to learn tumor characteristics within manually delineated tumor regions. Voxel-level radiomics feature maps were generated within tumors and integrated with CT images for dual-input co-training. Using the same dual-input, a cross-dataset transfer learning strategy was then used to adapt the pre-trained models to the immunotherapy context by fine-tuning. The model’s performance was evaluated using the concordance index (C-index), time-dependent area under the receiver operating characteristic curve, Kaplan-Meier survival analysis, calibration curves, and decision curve analysis. Additionally, Gradient-weighted Class Activation Mapping (Grad-CAM) was employed to suggest a possible interpretation of the model’s decision logic.ResultsThe proposed model demonstrated robust generalization ability. In the independent immunotherapy testing dataset, the model achieved a C-index of 0.73 (95% CI:0.63-0.82). The time-dependent AUCs for predicting 1-year and 2-year OS were 0.73 and 0.70, respectively. Calibration curves showed good agreement between predicted and observed survival probability. Stratification analysis showed distinct survival differences, with the high-risk group exhibiting significantly poorer OS compared to low-risk group (P<0.001).ConclusionWe developed a voxel-level deep radiomics framework that bridges the data gap in immunotherapy research through fine-tuning on a limited immunotherapy dataset, and subsequent validation on an independent immunotherapy testing dataset, demonstrating robust generalizability.
This secondary analysis of a randomized clinical trial reports the long-term survival rates and cancer- and noncancer-related causes of death associated with concurrent chemoradiotherapy with S-1 in older patients in China. QuestionIs concurrent chemoradiotherapy (CCRT) with S-1 associated with differences in survival compared with radiotherapy alone in older patients with esophageal cancer (EC)?FindingsIn this secondary analysis of a randomized clinical trial involving 298 patients with EC, the first prospective long-term data (median follow-up of 87 months) on treatment outcomes were reported. Patients in the CCRT with S-1 group showed significantly better overall survival than those in the RT-alone group, and long-term follow-up revealed no increase in noncancer-related mortality among patients receiving CCRT with S-1.MeaningThese results support CCRT with S-1 as an effective and tolerable treatment option for older patients with EC, addressing the critical evidence gap for this underrepresented population. ImportanceMost older patients with esophageal cancer (EC) are unable to complete standard platinum-based concurrent chemoradiotherapy (CCRT) due to reduced organ reserve, comorbidities, and malnutrition. A new treatment option-CCRT with S-1-has been found to have high efficacy and fewer toxic effects for this population, yet long-term data supporting its use remain limited.ObjectiveTo evaluate the long-term outcomes of CCRT with S-1 vs radiotherapy (RT) alone in older patients with EC.Design, Setting, and ParticipantsThis secondary analysis of a phase 3 randomized clinical trial conducted at 23 centers in China was not prespecified in the trial protocol. Patients aged 70 to 85 years with histologically confirmed EC were enrolled between June 1, 2016, and August 31, 2018. Data cutoff date was February 1, 2025, with an additional follow-up of 54 months beyond the primary analysis. Data were analyzed from February 1 to April 1, 2025.InterventionsPatients were randomly assigned 1:1 to receive CCRT with S-1 consisting of 54 Gy in 30 fractions with S-1, 70 mg/m2 per day on days 1 to 14 and 29 to 42, or RT alone consisting of 60 Gy in 30 fractions, 2.0 Gy per day 5 days per week.Main Outcomes and MeasuresThe primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), cause-specific mortality, cumulative incidence of death from EC or other reasons, and cumulative incidences of locoregional or distant metastasis during treatment or relapse after treatment.ResultsA total of 298 patients (median [IQR] age, 77 [74-79] years; 180 males [60.4%]) were enrolled. There were 151 patients (50.7%) clinically diagnosed with stage III to IV disease. With a median (IQR) follow-up of 87 (85-92) months, the median OS was 24.7 (95% CI, 21.2-37.6) months in the CCRT group and 15.1 (95% CI, 12.4-18.6) months in the RT group (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; P = .005). The 5-year OS rates were 33.5% (95% CI, 26.7%-42.1%) and 24.4% (95% CI, 18.3%-32.4%) for the CCRT and RT groups, respectively; the 8-year OS rates were 26.2% and 16.1%, respectively. The median PFS was 18.7 (95% CI, 13.1-25.8) months in the CCRT group and 9.2 (95% CI, 7.9-12.7) months in the RT group (HR, 0.69; 95% CI, 0.54-0.90; P = .005). Cause-specific analyses showed reduced EC-related mortality with CCRT (HR, 0.67; 95% CI, 0.50-0.89; P = .005), with 8-year absolute risks of 58.5% vs 72.9%, respectively, and no excess noncancer-related mortality.Conclusions and RelevanceIn this secondary analysis of a randomized clinical trial, long-term results showed that CCRT with S-1 was associated with a sustained survival benefit compared with RT alone, without increased noncancer-related mortality. This finding supports CCRT with S-1 as the preferred regimen for patients aged 70 to 85 years with EC.Trial RegistrationClinicalTrials.gov Identifier: NCT02813967
Long noncoding RNAs (lncRNAs) play crucial roles in regulating chromatin dynamics and gene expression, and their dysregulation is closely linked to tumorigenesis. However, their specific functions in gastric cancer (GC) remain poorly understood. Here, we found that lncRNA solute carrier family 16 member 1 antisense RNA 1 (SLC16A1-AS1) was markedly overexpressed in GC through integrated RNA sequencing (RNA-seq) analysis and validation in clinical tissues. High SLC16A1-AS1 expression correlated with advanced cancer stage, greater invasion depth, and poorer patient prognosis. Functional assays showed that SLC16A1-AS1 overexpression promoted GC cell proliferation, whereas knockdown inhibited proliferation in vitro and in vivo. Mechanistically, SLC16A1-AS1 interacted with the 5-methylcytosine (m5C) methyltransferase NOL1/NOP2/ SUN (NSUN2), enhancing m5C modification of GRP78 mRNA, which stabilized the transcript and increased GRP78 protein levels. Rescue experiments demonstrated that GRP78 overexpression reversed the proliferation-inhibitory effect of SLC16A1-AS1 depletion. These findings reveal that SLC16A1-AS1 drives GC cell proliferation via NSUN2-mediated m5C modification of GRP78 mRNA, suggesting a potential target for GC diagnosis and therapy.
Abstract Breast cancer is the most common malignancy among women worldwide. Estrogen receptor α (ERα)-positive breast cancer is about 70% in the total breast cancer. It has variable prognosis and high recurrent risk, frequently developing resistance to endocrine therapies. Herein, we have identified that a homeobox transcription factor MSX2 downregulated in ERα-positive breast cancer is correlated with the advanced grade and poor survival outcomes. Our results have demonstrated that MSX2 interacts with ERα to inhibit ERα-mediated transactivation. Mechanistically, MSX2 associates with HDAC1/HDAC2 to form a protein complex. MSX2 is required for recruitment of HDAC1/HDAC2 complex to estrogen response elements (EREs) region on ERα downstream target genes, reducing histone H3K9ac and H3K27ac levels to inactivate gene transcription. Functionally, ectopic expression of MSX2 suppresses cell growth and enhances the sensitivity to anti-estrogen treatment in ERα-positive breast cancer cells. Our results indicate that MSX2 as a novel co-repressor of ERα is involved in suppression of ERα-positive breast cancer progression. Restoring MSX2 protein may provide a promising strategy to overcome endocrine resistance in ERα-positive breast cancer.
With the increasing incidence of medication-related osteonecrosis of the jaw (MRONJ), the choice of reconstruction method for mandibular stage 3 MRONJ remains controversial. This study aimed to compare the outcomes of fibula flap (FF) and soft tissue flap with reconstruction plate (SR) in patients with mandibular stage 3 MRONJ. This retrospective cohort study included patients diagnosed with mandibular stage 3 MRONJ who underwent reconstruction between September 2018 and May 2024. Patients were categorized into the FF and SR groups. Demographic and general characteristics, intraoperative and postoperative outcomes, and oral health-related quality of life (OHRQoL) were compared between the two groups. Microsurgical outcomes of the FF group were also analyzed. A total of 29 patients (17 FF vs. 12 SR) were analyzed. The operative time was significantly shorter in the SR group (P < 0.001). A lower rate of wound-related complications and a greater improvement in OHRQoL were observed in the FF group compared to the SR group, although the differences were not statistically significant (P > 0.05). The FF group achieved significantly better plate-related complication-free survival (HR = 0.12, 95
KAT6 A (lysine acetyltransferase 6 A) is a member of the MYST family of histone acetyltransferases (HATs) that plays a pivotal role in regulating gene expression through the acetylation of histones and non-histone proteins. Dysregulation of KAT6A has been implicated in various cancers, making it an attractive target for therapeutic intervention. Over the past, significant advancements have been made in the development of small-molecule KAT6A inhibitors. PF-07248144 has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer models and is currently undergoing clinical evaluation. The development of these inhibitors has been facilitated by structure-based drug design and high-throughput screening, enhancing their selectivity and pharmacokinetic properties. This review provides a comprehensive overview of the structural and biological functions of KAT6A, its role in tumor progression, and the therapeutic potential of its inhibition. It summarizes the advancements in KAT6A inhibitor development from 2019 to the present, emphasizing the optimization processes from lead compounds to clinical candidates.
ObjectiveThis meta-analysis aimed to assess the prognostic value of circulating tumor DNA (ctDNA) in predicting progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), thereby providing evidence-based support for clinical decision-making.MethodsSix major English and Chinese databases (PubMed, Embase, Cochrane Library, etc.) were scanned from inception to August 2025. Studies evaluating the association between ctDNA and survival outcomes in advanced NSCLC patients receiving ICIs were included. Thirty-one eligible studies (2,107 patients) were selected following predefined criteria. Study quality was evaluated using Cochrane RoB-2 and the Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using random/fixed-effects models. Heterogeneity was assessed via Cochran’s Q test and I2 statistics. Subgroup analyses, sensitivity tests, and funnel plots were conducted to evaluate robustness and publication bias.ResultsPatients with undetectable ctDNA at baseline showed significantly prolonged PFS (HR = 0.49, 95% CI: 0.34–0.70, P < 0.01) and OS (HR = 0.45, 95% CI: 0.32–0.65, P < 0.01). Patients achieving ctDNA reduction or response during treatment exhibited substantial PFS (HR = 0.27, 95% CI: 0.21–0.35, P < 0.01) and OS (HR = 0.23, 95% CI: 0.17–0.31, P < 0.01) benefits, with complete molecular response (100% reduction in variant allele frequency, VAF) demonstrating the strongest predictive power, characterized by the lowest heterogeneity and favorable HRs for PFS (HR = 0.27, 95% CI: 0.18–0.41, P < 0.01) and OS (HR = 0.19, 95% CI: 0.12–0.29, P < 0.01). Subgroup analyses revealed three key patterns: superior predictive value in combination therapy versus monotherapy; higher sensitivity of next-generation sequencing (NGS) over digital polymerase chain reaction (PCR); and enhanced predictive power in later-line therapy compared to first-line therapy. Sensitivity analyses confirmed the stability of the results.ConclusionBaseline ctDNA status and early dynamic changes are reliable prognostic indicators in advanced NSCLC patients receiving ICI therapy, particularly in combination regimens and cases achieving complete molecular clearance. These findings support ctDNA as a biomarker for personalized treatment strategies.Clinical Trial Registrationhttps://www.crd.york.ac.uk/PROSPERO, CRD420251025308.
[This corrects the article DOI: 10.3389/fimmu.2026.1787518.].
Patients with stage II/III colorectal cancer remain at substantial risk of early postoperative recurrence, yet accurate risk stratification remains challenging. Here, we developed a dual-modal pathomics model integrating hematoxylin-eosin and Ki-67 whole-slide images to predict early recurrence in 362 patients from two medical centers. Among multiple pretrained feature encoders, the integrated hematoxylin-eosin plus Ki-67 model using the UNI encoder achieved the best performance, with an area under the curve of 0.902 in the external validation cohort. The model consistently stratified patients into distinct prognostic groups across clinical subgroups. Attention map visualization further suggested that high-risk predictions were associated with tumor invasive fronts, whereas low-risk predictions were linked to immune infiltration and fibrotic stromal regions. These findings highlight the potential of multimodal pathology artificial intelligence for clinically interpretable prognostic assessment and personalized postoperative management in colorectal cancer.
e15539 Background: To improve outcomes for patients with advanced colorectal cancer, chemotherapy can be combined with anti-VEGF and anti-EGFR agents. This study aimed to evaluate the efficacy and safety of fruquintinib in combination with irinotecan and capecitabine as a second-line treatment for patients with advanced colorectal cancer. Methods: This is a prospective, single-arm, real-world observational trial, enrolled patients aged 18 to 75 years with histologically confirmed metastatic colorectal adenocarcinoma. Eligible participants were those with second-line metastatic colorectal adenocarcinoma who had experienced failure with first-line standard therapy (recurrence within six months after the completion of adjuvant chemotherapy was classified as first-line treatment failure). All patients received treatment with fruquintinib (4 mg, po, qd, day 1-14) plus irinotecan (180 mg/m², ivgtt, day 1) (Note: 150 mg/m² for patients with UGT1A1*28 and UGT1A1*6 homozygous or double heterozygous variants) and capecitabine (1000 mg/m², po, bid, day 1-14) of each 21-day cycle. Irinotecan was discontinued after 6–8 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. An exploratory endpoint assessed changes in biomarkers and their impact on the immune microenvironment during treatment. Results: Between November 10, 2023, and November 20, 2024, 17 patients were enrolled and received treatment. At baseline, the median age was 63 years (range, 54–71 years), and 52.9% of the patients were male. ECOG PS 0/1 was 94.1%(16/17), and the primary tumor site was right-sided colon in 23.5% (4/17), left-side colorectum in 29.4% (5/17), and rectum in 47.0% (8/17). Of the 15 patients who completed at least one efficacy assessment, 1 patient (6.6%) achieved a partial response (PR), 6 patients (40.0%) had stable disease (SD), and 5 patients (33.3%) experienced disease progression (PD). The ORR was 26.7% (95% CI, 4–15), and the DCR was 60.0% (95% CI, 9–15). The median PFS was 9.53 months (95% CI, 7.66–NA). The most frequent grade 3/4 TRAEs were neutropenia (3/17, 17.6%), thrombocytopenia (2/17, 11.8%), and diarrhea (2/17, 11.8%). Conclusions: These results show the preliminary efficacy and safety of fruquintinib in combination with irinotecan and capecitabine as a second-line treatment for patients with advanced colorectal cancer. Clinical trial information: NCT06169202 .
Gastric cancer (GC) remains a global clinical challenge due to late diagnosis, high heterogeneity, and poor prognosis. Tumor stemness has emerged as a key factor driving tumor aggressiveness and therapeutic resistance. However, the systematic characterization of high-stemness GC cells and their molecular features remains limited. We integrated single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data to identify and characterize high-stemness GC cells. Stemness scores were calculated using CytoTRACE, and malignant cells were classified into high stemness (top 25% CytoTRACE-scored cells, HighStem), dynamic transition stemness (DTStem), and low stemness (LowStem) subpopulations based on the quartile method cutoff. ScPagwas and cell-cell communication profiling were used to explore genomic instability, genetic susceptibility, and microenvironmental interactions. HighStem-specific co-expression modules were identified via high-dimensional WGCNA (hdWGCNA), and features were screened using six machine learning algorithms. A benchmark model was constructed for HighStem prediction and interpreted using SHAP analysis. HighStem GC cells exhibited enhanced intercellular signaling, metabolic reprogramming, and stemness-related pathway activity. Five genes-APMAP, MAPRE1, GLB1, TSPAN6, and CDKN2A-were identified as robust HighStem features. Spatial and bulk transcriptomic validation confirmed their tumor-specific expression and prognostic relevance. The Support Vector Machine (SVM) model incorporating these genes achieved high accuracy (AUC = 0.973) in distinguishing HighStem cells, demonstrating strong clinical utility at the scRNA-seq level. In addition, experimental validation through knockdown of core genes (APMAP, CDKN2A, TSPAN6, MAPRE1, and GLB1) in SGC7901 and HGC-27 gastric cancer cell lines revealed a significant reduction in JAK1-STAT3 pathway activity, supporting their functional involvement in tumor stemness regulation. Furthermore, knockdown of these genes increased the sensitivity of GC cells to chemotherapeutic agents like 5-FU and cisplatin, indicating their potential role in chemoresistance. This study provides a comprehensive molecular and functional characterization of high-stemness GC cells. The identified signature genes and predictive models offer novel insights into GC stemness biology and could guide personalized therapeutic strategies. Furthermore, our findings suggest that the core genes identified in this study may serve as potential biomarkers for predicting treatment outcomes and monitoring therapeutic resistance in GC.
This study aims to examine the recurrence patterns in patients with locally advanced esophageal squamous cell carcinoma who underwent surgery following neoadjuvant chemotherapy combined with immunotherapy. Retrospective analysis of patients with esophageal squamous cell carcinoma who received neoadjuvant Chemo-IO before surgery at Zhejiang Cancer Hospital between 2019 and 2023. The clinicopathological features, recurrence patterns, overall survival (OS), and disease-free survival (DFS) were analyzed, and the impact of postoperative adjuvant radiotherapy on prognosis was evaluated. In total, 422 patients were included in the study. After a median follow-up of 22 months, disease recurrence was observed in 89 (21.1%) patients, comprising 37 cases (8.8%) of locoregional recurrence, 30 cases (7.1%) of distant metastasis, and 22 cases (5.2%) of combined recurrence. Patients who achieved a pathologic complete response demonstrated significantly higher 3-year OS rates (90.0% vs. 72.5%; P = 0.01) and DFS rates (73.2% vs. 61.8%; P = 0.046). Univariable and multivariable analyses identified pathological lymph node staging (ypN0 vs. ypN+; HR: 1.73; 95% CI: 1.01-2.99; P = 0.047) as an independent prognostic factor for locoregional recurrence. Kaplan-Meier curves for OS and DFS demonstrated that postoperative radiotherapy (PORT) significantly improved OS and DFS in ypN+ patients after propensity score matching. Additionally, PORT significantly enhanced locoregional recurrence-free survival and distant recurrence-free survival in ypN+ patients. In patients receiving neoadjuvant Chemo-IO, locoregional recurrence is the predominant recurrence pattern. For ypN+ patients, PORT significantly improved survival outcomes. However, long-term outcomes require further investigation through randomized controlled trials.
The use of sutures for stable wound closure in the humid, microbiologically complex oral environment is critical for mucosal healing. However, traditional absorbable sutures often loosen due to oral movements, leading to micro-gaps and accelerated microbial colonization, which disrupts healing. Inspired by spider silk's "expansion-induced supercontraction" in humidity, this study develops tea polyphenols self-contracting sutures to enhance mechanical reinforcement and repair efficiency. This next-generation degradable suture features a spider silk-inspired elastic network: polyvinyl alcohol (PVA) chains provide entropy-driven elastic recovery, while an ion-crosslinked network of sodium alginate and Ca²⁺ serves as a moisture-responsive unit. When dry, the network maintains pre-tension. Upon hydration, water molecules competitively coordinate with alginate and Ca²⁺, reducing crosslink density. This allows the PVA network to actively contract within four hours post-surgery, approximating wound edges, minimizing gaps, and reducing bacterial invasion. This next-generation degradable suture exhibits robust antibacterial activity, with 90.3 % inhibition against E. coli and 95.6 % against S. aureus. It also exerts significant biological regulation: compared to controls, it upregulates anti-inflammatory IL-10 expression by 2.41-fold, enhances oxidative stress scavenging capacity by 1.87-fold, and promotes angiogenesis. In vivo tests on difficult oral wounds show this next-generation degradable suture accelerates healing, reduces scarring, and improves tissue regeneration quality, especially in infected wounds. It holds broad potential for minimally invasive oral and maxillofacial surgeries and infection-prone wound repair.
Background:Synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC), characterized by a limited number of metastases at diagnosis, represents a significant subset of esophageal squamous cell carcinoma. However, the optimal treatment modality for the condition has not been determined. Therefore, we aimed to evaluate the efficacy of local consolidative radiotherapy (cRT) for the primary tumor combined with first-line chemoimmunotherapy (CIT). Methods:This retrospective cohort study included 102 patients with SOESCC who underwent first-line CIT, either alone or in combination with cRT, between 2018 and 2022. We analyzed the progression-free survival (PFS) and overall survival (OS) in the two groups using propensity score matching (PSM). Univariate and multivariate Cox regression analyses were performed to identify prognostic factors associated with PFS and OS. Failure patterns were compared between groups. Results:Patients who received the additional cRT had longer PFS (median PFS, 11.5 vs. 8.3 months, P = 0.009) than did those who received CIT only; however, no significant difference was noted in OS (median OS, 20.0 vs. 17.0 months, P = 0.410) between the two groups. These results remained consistent after PSM and multivariate Cox regression analyses (PFS: hazard ratio [HR] 0.539, 95% confidence interval [CI], 0.312-0.932, P = 0.027; OS: HR, 0.580, 95% CI, 0.307-1.095, P = 0.093). Notably, the pattern of failure in the CIT group was primarily characterized by locoregional failure, in contrast to the distant failure observed in the CIT + cRT group. Locoregional failure-free survival in the CIT + cRT group was significantly lower than that in the CIT group (P < 0.001). Moreover, no statistically significant difference was observed in the incidence of treatment-related adverse events between the two groups. Conclusions:In patients with SOESCC, the combination of local cRT and first-line CIT prolonged PFS without increasing treatment-related toxicity. In addition, cRT for primary tumor significantly reduced the incidence of locoregional failure. This synergistic approach appears to be a viable and potentially superior treatment strategy for the treatment of SOESCC.
Biliary tract malignancies are highly lethal, with a 5-year overall survival (OS) rate of less than 10%. This report describes a patient with HER2-positive advanced gallbladder cancer who achieved an OS of 90 months through multidisciplinary interventions and anti-HER2 targeted therapy. The patient achieved a prolonged period of disease stability, who was treated with various anti-HER2 targeted therapy, such as trastuzumab combined with pyrotinib and HER2-targeted antibody-drug conjugate (ADC). The patient received multiple local treatments (e.g., surgery, cryoablation, CyberKnife, and particle implantation) to further control the disease progression. Dynamic CA199 levels paralleled the treatment efficacy. This report underscores the significance of molecular profiling-guided personalized therapy and integrated multidisciplinary management in the treatment of biliary tract cancers.
Mantle cell lymphoma (MCL) is a rare, highly invasive non-Hodgkin's lymphoma. The main pathogenesis of MCL is associated with the formation of the IgH/CCND1 fusion gene and nuclear overexpression of cyclin D1, which accelerates the cell cycle, leading to tumorigenesis. The prognosis with current standard chemotherapy is still unsatisfactory. SQSTM1/p62 is a multifunctional adaptor that plays an important role in various tumors. Here, we found that the expression of p62 in MCL tissues was higher than that in hyperplastic lymphadenitis patients. Patients with low p62 expression in MCL cells had better overall survival and progression-free survival rates than those with high expression (p = 0.024 and p = 0.025, respectively). Multivariate Cox analysis indicated that the calculated death risk (hazard ratio [HR]) in patients with high expression levels of p62 increased to 2.742 (95
Slow Distributed Denial of Service attack (SL-DDoS) is a kind of server denial of service attack that exploits the vulnerability of HTTP protocol. Since SL-DDoS attacks do not need to send flooding or a large number of HTTP requests, it is difficult for traditional intrusion detection methods to detect such attacks, especially when HTTP traffic is encrypted. To overcome the above problems, this paper proposes an encrypted SL-DDoS attack detection and mitigation method based on the Multi-granularity Feature Fusion (MFFSL-DDoS) for Software Defined Networking (SDN). This method analyzes the encrypted session flow from the time sequence of packets and the spatiality of session flow and uses different deep learning methods to extract features, to obtain more effective features for abnormal traffic detection. In addition, this paper uses the advantages of SDN architecture to perform real-time defense against SL-DDoS attacks by way of SDN controller send flow tables. The experimental results show that the MFFSL-DDoS model has a higher detection rate than advanced methods, and can mitigate SL-DDoS attack traffic online and in real-time.
Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid-related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies.
Background: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is still the standard treatment mode for esophageal cancer (EC), but the rate of distant metastasis and local recurrence of this triple mode is still high. Distant metastasis is the main recurrence pattern. Therefore, there is an urgent need to explore a new treatment model to improve pathologic complete response (pCR) and patient survival. In recognition of the rise of immunotherapy, this study aimed to investigate the efficacy and safety of nCRT combined with immunotherapy (nRCIT) in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 22 patients with locally advanced ESCC were enrolled at our institution between 2019 and 2021. The patients underwent nRCIT therapy. The primary endpoint was pCR; secondary endpoints included major pathologic response (MPR), 1- and 2-year overall survival (OS) and disease-free survival (DFS), and adverse events (AEs). Meanwhile, we enrolled 53 patients with ESCC who underwent nCRT at our institution as the control group between 2012 and 2019. A 1:1 propensity score matching (PSM) with a caliper 0.374 was performed to balance potential bias. Results: In present work, 17 patients successfully completed nRCIT and esophagectomy, among whom index (BMI), clinical T stage, lymph node staging, tumor-node-metastasis (TNM) staging, and cycles of chemotherapy were comparable between groups. After the operation, 7 patients (41.2%) achieved pCR in both primary tumors and lymph nodes. Anastomotic leakage occurred in 3 patients (17.6%) and 1 patient succumbed to pneumonia during the perioperative period. Leukopenia was observed in 20 patients (90.9%) during neoadjuvant therapy, with grade 3 or higher AEs. The 1- and 2-year OS rates are 88.2% and 65.0%, respectively, in the nRCIT group, whereas 34.1% of patients achieved pCR, with 1- and 2-year OS rates of 82.3% and 68.6%, respectively, in the nCRT group. A significant MPR was observed in 10 out of 17 patients (58.8%) in the nRCIT group. Conclusions: nRCIT may appear to be safe and feasible for locally advanced ESCC.