Background: The accumulation of reactive oxygen species (ROS) in tumor microenvironment (TME) is an important player for tumorigenesis and progression. We aimed to explore the outcomes of ROS on tumor vessels and the potential regulated mechanisms. Methods: Exogenous H₂O₂ was adopted to simulate the ROS setting. Immunofluorescence staining and ultrasonography were used to assess the vascular endothelial coverage and perfusions in the tumors inoculated with Lewis lung cancer (LLC) and melanoma (B16F10) cells of C57BL/6 mice, respectively. ELISA and western-blot were used to detect the expression of secreted acidic and cysteine-rich protein (SPARC) and Caveale-1 in human umbilical vein endothelial cells (HUVEC) extra- and intracellularly. Intracellular translocation of SPARC was observed using electron microscopy and immunofluorescence approaches. Result: Under the context of oxidative stress, the pericyte recruitment of neovascularization in mouse lung cancer and melanoma tissues would be aberrated, which subsequently led to the disruption of the tumor vascular architecture and perfusion dysfunction. In vitro, HUVEC extracellularly SPARC was down-regulated, whereas intracellularly it was up-regulated. By electron microscopy and immunofluorescence staining, we observed that SPARC might undergo transmembrane transport via caveale-1-mediated endocytosis. Finally, the binding of SPARC to phosphorylated-caveale-1 was also detected in B16F10 tissues. Conclusion: In the oxidative stress environment, neovascularization within the tumor occurs structural deterioration and decreased perfusion capacity. One of the main regulatory mechanisms is the migration of extracellular SPARC from the endothelium to intracellular compartments via Caveolin-1 carriers.

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL. To develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index) and calibration curve. The 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010). The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysis showed that age >60 years, ECOG performance status score ≥2, elevated lactate dehydrogenase (LDH) level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year OS rate; age >60 years, elevated LDH level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year PFS rate. The nomogram included the primary site and regional lymph node involvement based on multivariate analysis. The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates, and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634, respectively. The primary site and regional lymph node involvement are independent prognostic factors for early-stage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

An epileptic seizure is the external manifestation of abnormal neuronal discharges, which seriously affecting physical health. The pathogenesis of epilepsy is complex, and the types of epileptic seizures are diverse, resulting in significant variation in epileptic seizure data between subjects. If we feed epilepsy data from multiple patients directly into the model for training, it will lead to underfitting of the model. To overcome this problem, we propose a robust epileptic seizure detection model that effectively learns from multiple patients while eliminating the negative impact of the data distribution shift between patients. The model adopts a multi-level temporal-spectral feature extraction network to achieve feature extraction, a feature separation network to separate features into category-related and patient-related components, and an invariant feature extraction network to extract essential feature information related to categories. The proposed model is evaluated on the TUH dataset using leave-one-out cross-validation and achieves an average accuracy of 85.7%. The experimental results show that the proposed model is superior to the related literature and provides a valuable reference for the clinical application of epilepsy detection.

Background: Limited evidence supports the omission of routine bone marrow (BM) examination (biopsy and aspiration) in patients with nasal‐type extranodal NK/T‐cell lymphoma (ENKTCL). This study was aimed at assessing whether BM examination provides valuable information for positron emission tomography/computed tomography (PET/CT)–based staging in this patient population.Patients and Methods: Patients newly diagnosed with ENKTCL who underwent initial staging with both PET/CT and BM examination between 2013 and 2020 were retrospectively identified in two Chinese institutions. Overall, 742 patients were included; the BM examination was positive in 67 patients.Results: Compared with BM biopsy alone, the combination of BM biopsy and aspiration assessment did not afford any additional diagnostic value. No patient with a positive BM biopsy was found to have early‐stage disease by PET/CT. BM biopsy or PET/CT led to upstaging from stage III to IV as a result of BM involvement in 21 patients. In 135 patients with distant organ involvement, BM involvement was associated with worse overall survival (OS) and progression‐free survival (PFS) compared with the corresponding durations in patients without BM involvement (2‐year OS: 35.9% vs. 60.4%, p < .001; PFS: 26% vs. 40.7%, p = .003). No difference in survival was noted between groups judged positive based on PET/CT and BM biopsy.Conclusion: Compared with aspiration, BM biopsy led to the detection of more BM lesions. Baseline PET/CT can be safely used to exclude BM involvement in early‐stage disease. Overall, routine BM examination affords diagnostic or prognostic value over PET/CT in patients with advanced‐stage nasal‐type ENKTCL.

Background Despite 3-year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression-free survival at 3 years (3-year PFS) and overall survival (OS) among patients with ESCC. Methods We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age- and sex-matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data. Results The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3-year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5-year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9-17.5). Conversely, the SMR for patients who achieved 3-year PFS was 0.9 (95% CI, 0.6-1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88-0.90). The strongest correlation was observed between 3-year PFS and 5-year OS in RCTs and retrospective studies. Conclusions Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3-year PFS had excellent outcomes. Our study supports 3-year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC.

Primary small cell carcinoma of the oesophagus (PSCCE) is a gastrointestinal tumour of rare onset. The current study was to investigate the role of a novel risk stratification system (RSS) for PSCCE. The study included patients with PSCCE attending any of five medical institutions in China in 2008–2021, four of which served as a training set (n = 422) for construction of the RSS while the other served as a separate cohort (n = 256) for validation of the model. The RSS was established based on covariates associated with overall survival (OS) with a two-sided P-value of < 0.05 in multivariable regression. Survival discrimination of RSS was assessed. In the training cohort, multivariate regression analysis revealed age, Eastern Cooperative Oncology Group score, and initial lymph node metastasis to be independent prognostic factors for OS in non-distant metastatic PESCC; concurrent hepatic metastasis was the only significant predictor of distant metastatic PESCC. Accordingly, the RSS was developed and could classify patients into four subgroups: low-risk localized disease (LLD, defined as non-distant metastasis PESCC without risk factors, n = 58); high-risk localized disease (HLD, defined as non-distant metastasis PESCC with ≥ 1 risk factor, n = 199); low-risk metastatic disease (LMD, defined as metastatic PESCC without concomitant liver metastases, n = 103); and high-risk metastatic disease (HMD, definded as metastatic disease with synchronous liver metastases, n = 63). Three-year OS rates were 52.5%, 29.5%, 14.4%, and 5.7% for LLD, HLD, LMD, and HMD, respectively. When compared with the tumor-node-metastasis (TNM) system, RSS showed a consistently superior ability to predict OS in both the training and validation cohorts. The RSS is a reliable stratification model that could be used to optimize treatment for PESCC.