Aims: Antibody-negative type 1 diabetes (T1D) is a provisional diagnosis with unclear etiology. This study aimed to determine the prevalence and phenotypic characteristics of monogenic diabetes within a large antibody-negative T1D cohort. Methods: A total of 482 antibody-negative T1D patients were included from a clinically diagnosed T1D cohort. Targeted sequencing using a custom gene panel covering 36 genes and the mitochondrial 3243 A > G mutation was performed. Demographic, metabolic, and human leukocyte antigen (HLA) data were analyzed. Beta-cell function was assessed in patients with monogenic diabetes amenable to precision treatment. Results: Among 482 antibody-negative T1D patients, 2.5% (12/482) had maturity-onset diabetes of the young (MODY) and 1.7% (8/482) had mitochondrial diabetes. The prevalence of MODY increased to 11.1% (6/54) among childhood-onset patients with a single susceptible HLA haplotype, while mitochondrial diabetes reached 6.2% (7/113) in adult-onset patients lacking HLA-susceptible haplotypes. Other characteristics, including gender, age at diagnosis, hemoglobin A1c, 2-hour postprandial C-peptide (2hCP), and family history of diabetes, showed no significant differences. Compared with the "truly" antibody-negative T1D group, MODY patients had an earlier onset, whereas mitochondrial diabetes patients had later onset, higher 2hCP, and fewer HLAsusceptible haplotypes (all P < 0.05). Of eight recalled monogenic diabetes patients, 62.5% (5/8) retained random C-peptide > 100 pmol/L after a median 15.7 years. Conclusions: In antibody-negative T1D, MODY and mitochondrial diabetes accounted for 2.5% and 1.7%, respectively. HLA genotype was the key distinguishing factor. Persistent C-peptide secretion in monogenic diabetes supports the need for genetic screening in antibody-negative T1D patients.

Predicting the pathogenic potential of tandem repeat (TR) expansions is critical for understanding neurogenetic disorders but remains challenging due to data scarcity, extreme class imbalance, and complex sequence dependencies. Most existing approaches primarily rely on gene-centric signals, often overlooking intrinsic sequence properties that mechanistically modulate instability. This paper proposes TREPP, an interpretable ensemble learning framework designed to prioritize candidate high-risk TR loci. TREPP combines genomic location information with local sequence properties to represent the biological context of expansion. First, the framework extracts a comprehensive feature set including gene proximity, GC content differences, and local repeat density patterns. Then, to mitigate label scarcity, TREPP employs a multi-sampling strategy that trains multiple CatBoost base learners on diversified negative subsets. Finally, a sparse logistic regression meta-learner aggregates the calibrated outputs of these base models to produce a final prioritization score. Experimental results on a curated benchmark dataset show that TREPP achieves an AUPRC of 94.71%, exceeding the state-of-the-art method RExPRT by 6.11 percentage points on the fixed benchmark split. Furthermore, interpretability and bias-control analyses support the interpretation that TREPP leverages biologically plausible signals, making it a useful prioritization framework for identifying candidate high-risk TR loci. TREPP is publicly available at https://github.com/minghuaxu/TREPP.

OBJECTIVES:Type 1 diabetes mellitus (T1DM) has become one of the major public health challenges in China. This study aims to construct an evaluation indicator system applicable to the standardized prevention and control work of T1DM demonstration management centers, so as to provide a scientific basis for evaluation and strategy optimization of prevention and control practices. METHODS:Based on the structure-process-outcome (S-P-O) model as the theoretical framework, a preliminary pool of evaluation indicators was established. The indicators were revised through the expert consultation method to form a preliminary draft of the evaluation indicator system. Subsequently, an expert consensus meeting was conducted using the nominal group technique (NGT) to determine the final evaluation indicator system. The analytic hierarchy process combined with expert scoring method was used to calculate the weight of each indicator. RESULTS:The positive response rate of experts participating in the consensus meeting was 100%, and the authority coefficient was 0.925. The Kendall's W coefficients for the importance, rationality, and accessibility of the indicators were 0.146 (P>0.05), 0.197 (P<0.05), and 0.319 (P<0.05), respectively. The final evaluation indicator system consisted of 3 first-level indicators, 15 second-level indicators, and 41 third-level indicators. Results of the analytic hierarchy process showed that the consistency ratios of all judgment matrices were <0.1, and the Kendall's W coefficient of the expert scoring method was 0.242 (P<0.05). The weights of the first-level indicators "structure" "process" and "outcome" were 0.287 7, 0.317 7, and 0.394 6, respectively. CONCLUSIONS:The evaluation indicator system for standardized prevention and control of T1DM can not only effectively evaluate the implementation of standardized prevention and control work in demonstration management centers, but also provide clear guidance for continuous improvement. This indicator system may be further optimized and refined in future practical applications.

AIMS:Despite its rising prevalence, older adults with Type 1 diabetes remain poorly characterised. This study aimed to characterise those over 60 years and quantify independent predictors of glycaemic control and complications. MATERIALS AND METHODS:We performed a multicentre analysis using real-world data from the China Diabetes Type 1 Study (CD1S), including 69 centres across China between 2016 and 2021. Patients were stratified into three age groups (≥ 60, 18-59 and < 18 years) for assessment of clinical characteristics and complications. Multiple regression examined associations of clinical features with HbA1c and complications. Variable importance was interpreted using SHAP values derived from a random forest model. RESULTS:We enrolled 9637 patients with Type 1 diabetes. Compared with young adults, older adults with Type 1 diabetes were less likely to achieve target HbA1c (7.2% vs. 10.2%, p < 0.05) and had a substantially higher burden of chronic complications, with 81.0% of older adults having at least one complication. Longer duration, higher BMI and higher gross domestic product (GDP) were significantly associated with lower HbA1c (all p < 0.05). Higher GDP was linked to reduced rates of diabetic retinopathy (19.7%), nephropathy (13.6%) and peripheral neuropathy (46.9%), yet a higher proportion of peripheral vasculopathy (41.8%) was observed compared with middle- and low-GDP regions. CONCLUSIONS:Older adults with Type 1 diabetes exhibit a unique clinical profile of poor glycaemic control and a high burden of complications, influenced by regional GDP disparities. This underscores the critical need to integrate socioeconomic factors into personalised care strategies to advance health equity. REGISTRATION NUMBER:NCT05498974.

Objective To assess the changes in the disease burden and risk factors of type 2 diabetes mellitus (T2DM) globally and in China from 1990 to 2021 and predict their future trends.Methods Based on the Global Burden of Disease 2021 database, the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized disability-adjusted life years (DALY) rate (ASDR), age-standardized mortality rate (ASMR), and their estimated annual percentage changes (EAPC) were used to analyze the disease burden of T2DM globally and in China from 1990 to 2021. The auto-regressive integrated moving average model (ARIMA) was applied to predict trends in disease burden.Results From 1990 to 2021, the global T2DM ASIR [EAPC=1.74%, 95%CI (1.72%, 1.76%)], ASPR [EAPC=2.12%, 95%CI (2.08%, 2.16%)], ASMR [EAPC=0.21%, 95%CI (0.15%, 0.27%)] and ASDR [EAPC=1.04%, 95%CI (1.00%, 1.08%)] showed increasing trends. In China, T2DM ASIR [EAPC=1.10%, 95%CI (1.01%, 1.19%)], ASPR [EAPC=1.65%, 95%CI (1.56%, 1.75%)], and ASDR [EAPC=0.69%, 95%CI (0.54%, 0.84%)] showed an upward trend, while ASMR [EAPC=-0.22%, 95%CI (-0.49%, 0.04%)] showed no significant change. The prevalence, DALY rate, and mortality of T2DM among the elderly were higher than those among young and middle-aged adults globally and in China, while the incidence rate among individuals aged 15 to 24 is notably elevated. Globally and in China, all four rates were higher in males than in females. From 1990 to 2021, high fasting plasma glucose and high body mass index (BMI) remained the top two risk factors for T2DM-related deaths globally and in China, while environmental particulate matter pollution showed the largest rise in ranking among risk factors. It is projected that by 2040, the global and China T2DM ASIR will rise to 385.85/100,000 and 305.10/100,000, respectively; ASPR to 8,619.18/100,000 and 7,509.98/100,000, respectively; ASDR to 975.50/100,000 person years and 636.63/100,000 person years, respectively; global ASMR will increase to 18.83/100,000, while China’s ASMR will decrease to 8.64/100,000.Conclusion The disease burden of T2DM was heavier in males and the elderly, and the onset age tended to be younger among adolescents. High fasting plasma glucose and high BMI were important risk factors for T2DM-related deaths globally and in China. China has achieved notable results in prevention and control, but the predicted disease burden remains severe. It is necessary to strengthen the three-level prevention strategy and strictly control relevant risk factors.

Background First-degree relatives (FDRs) of type 1 diabetes (T1D) patients are at high risk for T1D. Early screening enables timely intervention, yet participation remains suboptimal, missing opportunities in this high-risk group. Understanding determinants of screening participation and translating them into actionable, theory-informed, family-centered strategies is essential to optimize preventive care. Methods In this qualitative study in China, semi-structured interviews were conducted with 21 adult T1D probands or parents of pediatric T1D patients who have unaffected children. The Theoretical Domains Framework (TDF) guided data collection and analysis. Barriers were mapped to Behavior Change Techniques (BCTs). Results We identified 18 facilitators, 11 barriers, and 2 neutral factors, mapped across 12 TDF domains. Key barriers included limited awareness, misconceptions, cost, restricted medical resources, insufficient publicity, and anxiety; key facilitators included perceived benefits, optimism, health beliefs, and social support. Through TDF-BCT mapping, 34 intervention strategies were categorized into 13 categories targeting knowledge enhancement, environmental adaptation, social and emotional support, and self-efficacy building. Conclusions This study provides a systematic, theory-based analysis of factors influencing screening participation for T1D. The resulting strategy map offers a set of theory-informed, family-centered suggestions to guide nurses and educators in supporting parents and improving early detection in clinical practice, subject to future empirical validation. Implications for practice Nurses and educators should develop localized, family-centered screening promotion programs guided by theory-driven frameworks and BCTs. Concurrently, systemic enablers—such as resource allocation, financial support, and routine follow-up guidance—must be established to comprehensively address barriers to participation in screening.

OBJECTIVES:To evaluate the association between rewarming rate and short-term postoperative outcomes after repair of DeBakey type I acute aortic dissection (AAD). METHODS:From January 2019 to November 2023, 763 patients with DeBakey type I AAD undergoing total arch replacement (TAR) and the frozen elephant trunk (FET) procedure were enrolled. Patients were categorized into 3 groups according to bladder rewarming rate: high (≥0.5°C/min), medium (0.2-0.5°C/min), and low (≤0.2°C/min). Propensity score matching (PSM) was applied to balance baseline characteristics, and short-term postoperative outcomes were compared across groups. RESULTS:After PSM, the incidence of short-term death differed significantly across the 3 bladder rewarming rate groups (overall P value = .021). Pairwise comparisons showed a higher incidence of short-term death in the ≥0.5°C/min group compared with the 0.2-0.5°C/min group (Holm-adjusted P value = .041), whereas no significant differences were observed between other pairs. No significant differences were found in other major short-term postoperative outcomes. CONCLUSIONS:In patients with DeBakey type I AAD who undergo TAR and FET procedure, faster bladder rewarming (at ≥0.5°C/min) may increase the risk of short-term death, whereas slower rewarming (at ≤0.2°C/min) does not appear to adversely affect early postoperative outcomes. These findings should be interpreted with caution and underscore the need for further prospective investigation to define optimal rewarming strategies.

Identifying the complex genetic architecture of Alzheimer’s disease (AD) is critical for understanding its pathophysiology. While network-based computational methods assist in this task, they primarily model simple pairwise gene interactions and fail to capture the higher-order associations of genes that drive complex diseases. To address this limitation, we introduce HyperAD, a novel hypergraph neural network framework designed to predict AD risk genes by explicitly modeling these higher-order associations of genes. HyperAD constructs a hypergraph in which functional gene sets from databases such as MSigDB form hyperedges, and uses a two-stage hypergraph message passing neural network to extract high-order association information from the hypergraph. Comprehensive evaluations demonstrate that HyperAD significantly outperforms state-of-the-art methods. We validate the prediction results of HyperAD through multiple lines of evidence. HyperAD-predicted genes are enriched in AD-related biological processes and have significant associations with known related genes in terms of sequence similarity, protein interaction, and miRNA. In addition, their protein expression levels are significantly altered in the brains of AD patients, and they contain both known risk sites and new, high-confidence candidate genes. HyperAD provides a more accurate and biologically insightful tool for prioritizing genes and unraveling the complex genetic landscape of AD.

Patients with EGFR-positive non-small cell lung cancer (NSCLC) do not respond as well to immunotherapy as patients without an EGFR mutation. Nevertheless, recent studies indicate that subsequent immunotherapy following EGFR-TKI treatment may be effective in EGFR-positive NSCLC. Given the critical role of the tumor immune microenvironment (TIME) in determining immunotherapy efficacy, understanding the influence of EGFR-TKI on the TIME in NSCLC remains an important yet unresolved area of research. Single-cell RNA sequencing (scRNA-seq) was performed to investigate the TIME of NSCLC patients. Post-treatment samples were analyzed from three EGFR-positive NSCLC patients treated with neoadjuvant EGFR-TKI (Neo-TKI) and two EGFR-negative NSCLC patients treated with neoadjuvant immunotherapy (Neo-IO). The scRNA-seq datasets of seven EGFR-positive NSCLC patients undergoing surgery only (TN-TKI) from the National Genomics Data Center (CRA001477, CRA001963) and six EGFR-negative NSCLC patients received surgery only (TN-IO) from the Gene Expression Omnibus (GSE131907) were analyzed to assess the TIME in treatment-naïve conditions. A total of ∼173, 000 single cells were sequenced, revealing 6 subpopulations. Compared to TN-TKI samples, Neo-TKI samples showed a higher proportion of T and B cells, whereas the proportion of myeloid cells significantly decreased. Further analysis of T cell composition in Neo-TKI samples revealed a trend towards a higher prevalence of GZMK+CD8+T cells and enrichment of positive regulation of T cell activation pathway. The expression of TLS-associated genes in CD4+ T cells was significantly elevated, along with the upregulation of immune-related pathways, such as B cell activation signaling and IL-17-related signaling, underscoring the immunomodulatory role of EGFR-TKI. Regarding B cell composition, Neo-TKI samples showed a higher proportion of germinal center B cells with an enrichment in positive regulation of B cell signaling pathway compared to TN-TKI samples. Notably, a shift in tumor-associated macrophages from an M2 phenotype to a neutral phenotype was observed in Neo-TKI samples, supporting the notion that EGFR-TKI impacts the immune landscape. Further, we conducted an exploratory analysis comparing the effects of immunotherapy and EGFR-TKI treatment on the TIME. Distinct differences were observed in cellular subpopulation distribution, enriched genes, and activated pathways. Overall, EGFR-TKI therapy appears to have a more pronounced effect on the TIME of patients with NSCLC. EGFR-TKI therapy alleviated the immunosuppressive TIME of EGFR-positive NSCLC, providing valuable insights for optimizing subsequent immunotherapy strategies in EGFR-positive NSCLC. Fang Wu, Dan Fan, Yingzhe Zhang, Wenliang Liu, Fenglei Yu, Wen Hu, Yue Zeng, Yurong Peng, Chunhong Hu, Xianling Liu, Fang Ma, Chao Deng, Zhenhua Qiu, Shijiao Yao, Shuxing Wang, Xiaoqiao Lin, Aoxi Liang, Xinzhu Lin, Qian Guan, Han Yang, Yiyang Li. Neoadjuvant EGFR-TKI therapy reshapes tumor immune microenvironment in resectable EGFR-positive non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3278.

BACKGROUND:The hemoglobin glycation index (HGI) represents the discrepancy between the glucose management indicator (GMI) based on mean blood glucose levels and laboratory values of glycated hemoglobin (HbA1c). The HGI is a promising indicator for identifying individuals with excessive glycosylation, facilitating personalized evaluation and prediction of diabetic complications. However, the factors influencing the HGI in patients with type 1 diabetes (T1D) remain unclear. Autoimmune destruction of pancreatic β cells is central in T1D pathogenesis, yet insulin resistance can also be a feature of patients with T1D and their coexistence is called "double diabetes" (DD). However, knowledge regarding the relationship between DD features and the HGI in T1D is limited. AIM:To assess the association between the HGI and DD features in adults with T1D. METHODS:A total of 83 patients with T1D were recruited for this cross-sectional study. Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI. DD features included a family history of type 2 diabetes, overweight/obesity/central adiposity, hypertension, atherogenic dyslipidemia, an abnormal percentage of body fat (PBF) and/or visceral fat area (VFA) and decreased estimated insulin sensitivity. Skin autofluorescence of advanced glycation end products (SAF-AGEs), diabetic complications, and DD features were assessed, and their association with the HGI was analyzed. RESULTS:A discrepancy was observed between HbA1c and GMI among patients with T1D and DD. A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy (P = 0.030), particularly retinopathy (P = 0.031). Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI, compared with those without DD features (adjusted odds ratio = 8.12; 95% confidence interval: 1.52-43.47). Specifically, an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI. Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI. CONCLUSION:In patients with T1D, DD features are associated with a higher HGI, which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.

As hypothermic circulatory arrest (HCA) is being more frequently induced in patients undergoing aortic arch surgery, its safety at different degrees has become a crucial area of study. The aim of this study was to assess the surgical outcomes of mild hypothermic circulatory arrest (MI-HCA) during aortic arch surgery. Acute type A aortic dissection (ATAAD) patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) surgery between January 2014 and December 2023 were enrolled in this study. The patients were divided into two groups according to the minimum nasopharyngeal temperature: the moderate hypothermic circulatory arrest (MHCA) group (20–28 °C) and the MI-HCA group (> 28 °C). The inverse probability of treatment weighting (IPTW) was used to balance differences in the baseline characteristics. Perioperative variables were analysed via pairwise comparisons, multivariable logistic regression, and subgroup forest plots to assess the impact of MI-HCA on surgical outcomes. A total of 447 patients were included in this study, and the mean minimum nasopharyngeal temperature was 24.80 (23.98, 27.30) °C in the MHCA group and 30.10 (29.80, 30.70) °C in the MI-HCA group. The incidence of acute kidney injury (AKI) in the MI-HCA group was lower than that in the MHCA group (52

BackgroundInetetamab is a novel recombinant humanized anti-Human epidermal growth factor receptor 2 (HER2) monoclonal antibody. This real-world retrospective study assessed the efficacy and safety of inetetamab-containing regimens in first-line/second-line treatment of HER2-positive metastatic breast cancer (MBC).MethodsThis study retrospectively recruited HER2-positive MBC patients who received inetetamab- containing regimens from June 2020 to May 2023. The outcomes included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).ResultsA total of 329 patients were enrolled and included in the efficacy analysis. The most frequently used treatment strategy was contained inetetamab plus pyrotinib (205/329, 62.3%). Patients treated with first-line regimens benefited the most, with a median PFS of 15.0 versus (vs.) 10.0 months (first-line- vs. second-line inetetamab plus pyrotinib, p <0.001), 19.0 vs. 17.0 months (first-line- vs. second-line inetetamab plus pertuzumab, p=0.096), and 13.0 vs. not reached months (first-line- vs. second-line inetetamab plus chemotherapy, p=0.229). The complete response (CR) was observed in 16 (4.9%) patients of all cohort, with the ORR was 51.1% (95% confidence interval [CI], 45.7%-56.4%), and the DCR was 96.4% (95% CI, 93.7%-97.9%). The grade 3 or higher adverse events (AEs) were observed in 29.5% of the whole study cohort. Diarrhea (39.2%), white blood cell count decreased (33.0%), and myelosuppression (18.6%) as the most frequent ones.ConclusionsFollowing the first- and second-line of treatment, inetetamab- containing combinations demonstrated promising clinical activity and a manageable safety profile in patients with HER2-positive MBC, especially in the first-line treatment.

Inetetamab is a novel recombinant humanized anti-Human epidermal growth factor receptor 2 (HER2) monoclonal antibody. This real-world retrospective study assessed the efficacy and safety of inetetamab-containing regimens in first-line/second-line treatment of HER2-positive metastatic breast cancer (MBC). This study retrospectively recruited HER2-positive MBC patients who received inetetamab- containing regimens from June 2020 to May 2023. The outcomes included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 329 patients were enrolled and included in the efficacy analysis. The most frequently used treatment strategy was contained inetetamab plus pyrotinib (205/329, 62.3%). Of 329 patients for efficacy evaluation, the median PFS was 14.5 months. Patients treated with first-line regimens benefited the most, with a median PFS of 15.0 versus (vs.) 10.0 months (first-line- vs. second-line inetetamab plus pyrotinib, p <0.001), 19.0 vs. 17.0 months (first-line- vs. second-line inetetamab plus pertuzumab, p=0.096), and 14.0 vs. not reached months (first-line- vs. second-line inetetamab plus chemotherapy, p=0.229). The inetetamab plus pertuzumab group had the longest survival compared with inetetamab plus pyrotinib and inetetamab plus chemotherapy group in first-line (mPFS, 19.0 vs. 15.0 vs. 13.0 months) and second-line (mPFS, 17.0 vs. 10.0 vs. not reached months) settings. The ORR was 54.4% (95%CI, 49.0%-59.7%), with 14 (4.3%) complete response (CR) and 150 (45.6%) partial response (PR). Besides, 148 (45.0%) patients had stable disease (SD) for a disease control rate (DCR) of 99.4% (95%CI, 97.8%-99.8%). Grade 3 or higher adverse events (AEs) were observed in 29.5% of all 329 patients and mainly included diarrhea (38/329, 11.6%), white blood cell decreased (32/329, 9.7%), myelosuppression (18/329, 5.5%), neutrophil count decreased (7/329, 2.1%). No treatment-related deaths were reported. Compared with the other two subgroups, the incidence AEs of any grade (205/329, 62.3%) and grade ≥3 (80/329, 24.3%) in inetetamab plus pyrotinib group was the highest. Following the first- and second-line of treatment, inetetamab- containing combinations demonstrated promising clinical activity and a manageable safety profile in patients with HER2-positive MBC, especially in the first-line treatment. Citation Format: Yuxin Mu, Hui Zhang, Chao Deng, Jiao Yang, Lu Gan, Qingmo Yang, Xuefeng Xu, Wanping Liang, Xiaowei Qi, Liang Xu, Jian Zhang. Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer in first-line/second-line setting [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-03-14.

OBJECTIVES:Neoadjuvant immunotherapy has demonstrated favorable efficacy in patients with resectable non-small cell lung cancer (NSCLC). However, its clinical application remains limited by the lack of reliable and non-invasive biomarkers. Although existing histological biomarkers such as programmed death-ligand 1 (PD-L1) and tumor mutation burden (TMB) can be used for reference, they rely on invasive sampling and are susceptible to tumor heterogeneity. This study evaluated a series of peripheral blood inflammation-related indicators, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and interleukin-6 (IL-6), to explore their potential as non-invasive predictive and prognostic biomarkers for NSCLC. Furthermore, a prediction model based on the above indicators was constructed to provide a practical and feasible tool for optimizing individualized clinical management in patients with resectable NSCLC. METHODS:A retrospective analysis was conducted on 144 patients with resectable (stage IB-IIIB) NSCLC who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at the Second Xiangya Hospital, Central South University, between 2019 and 2022. Peripheral blood-related indicators at baseline and before surgery were collected. Clinical data that might influence treatment efficacy were also recorded, including age, sex, body mass index, smoking history, pathological type, clinical stage, and use of immune checkpoint inhibitors. The relationships between peripheral blood inflammatory indicators (NLR, LMR, PLR, SII, and IL-6) and objective response rate (ORR), pathological complete response (pCR), major pathological response (MPR), and disease-free survival (DFS) were analyzed. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values for each indicator. A prediction model for the efficacy of neoadjuvant immunotherapy in NSCLC was constructed using least absolute shrinkage and selection operator (LASSO) regression combined with a multivariate Cox proportional hazards model. RESULTS:The median age of included patients was 58 years, and 91.0% (131/144) were male. Among pathological types, squamous cell carcinoma accounted for 74.3% (107/144), adenocarcinoma for 22.9% (33/144), and other types for 4 cases. The overall ORR, pCR, and MPR rates were 69.2%, 42.4%, and 61.5%, respectively. Univariate analysis showed that patients with squamous cell carcinoma had significantly higher ORR (P=0.007), pCR (P=0.027), and MPR (P=0.019). Lower baseline LMR was associated with a higher ORR. Elevated baseline PLR was significantly associated with pCR (P=0.014) and MPR (P=0.043). Increased baseline SII (P=0.015) and IL-6 (P=0.043) were associated with higher MPR rates. Multivariate analysis showed that squamous cell carcinoma was an independent predictor of MPR (OR=7.34, 95% CI 1.02 to 52.51, P=0.047), and lower baseline LMR was an independent predictor of ORR in NSCLC (OR=0.21, 95% CI 0.05 to 0.92, cutoff value 3.12; P=0.04). Further survival analysis indicated that low baseline NLR (HR=0.363, P=0.014), low preoperative LMR (HR=0.260, P=0.018), and high preoperative SII (HR=0.278, P=0.003) significantly reduced the risk of DFS. A prediction model including 9 factors (age, pathological type, baseline NLR, baseline neutrophils, baseline IL-6, baseline monocytes, preoperative lymphocytes, preoperative SII, and preoperative LMR) was established for predicting the efficacy of neoadjuvant immunotherapy in NSCLC, with an AUC of 0.818. CONCLUSIONS:Neoadjuvant immunotherapy demonstrates favorable clinical efficacy in patients with NSCLC, particularly in those with squamous cell carcinoma. Meanwhile, peripheral blood inflammation-related indicators may serve as important biomarkers for predicting the efficacy and prognosis of neoadjuvant immunotherapy in NSCLC.

Identifying cancer genes is crucial for treatment and understanding pathogenesis. Recent methods typically leverage protein-protein interaction (PPI) networks or gene functional association data from annotated gene sets. There may be some shared neighborhood structure information between these two types of gene association data. While this common information may contain more accurate gene association information, existing methods often overlook this potential. To address this gap, we introduce DISFusion, which integrates multi-omics cancer data, PPI networks, and gene functional associations to identify cancer genes. A key innovation of DISFusion is the cross-view decorrelation loss, which enhances the common information between PPI networks and gene functional associations, thereby improving prediction accuracy. Extensive experiments indicate that DISFusion outperforms state-of-the-art methods and exhibits greater generalization ability. Moreover, analysis of CPTAC pan-cancer proteomic data highlights significant associations between the 30 novel cancer genes predicted by DISFusion and multiple cancer types, underscoring its practical utility. These findings validate the effectiveness of enhancing common information and provide new insights into cancer gene identification.