PyHFO: lightweight deep learning-powered end-to-end high-frequency oscillations analysis application.

OBJECTIVE: This study aims to develop and validate an end-to-end software platform, PyHFO, that streamlines the application of deep learning methodologies in detecting neurophysiological biomarkers for epileptogenic zones from EEG recordings. Methods: We introduced PyHFO, which enables time-efficient HFO detection algorithms like short-term energy (STE) and Montreal Neurological Institute and Hospital (MNI) detectors. It incorporates deep learning models for artifact and HFO with spike classification, designed to operate efficiently on standard computer hardware. Main results: The validation of PyHFO was conducted on three separate datasets: the first comprised solely of grid/strip electrodes, the second a combination of grid/strip and depth electrodes, and the third derived from rodent studies, which sampled the neocortex and hippocampus using depth electrodes. PyHFO demonstrated an ability to handle datasets efficiently, with optimization techniques enabling it to achieve speeds up to 50 times faster than traditional HFO detection applications. Users have the flexibility to employ our pre-trained deep learning model or use their EEG data for custom model training. Significance: PyHFO successfully bridges the computational challenge faced in applying deep learning techniques to EEG data analysis in epilepsy studies, presenting a feasible solution for both clinical and research settings. By offering a user-friendly and computationally efficient platform, PyHFO paves the way for broader adoption of advanced EEG data analysis tools in clinical practice and fosters potential for large-scale research collaborations.

Assessing anatomical variations of the inferior mesenteric artery via three-dimensional CT angiography and laparoscopic colorectal surgery: a retrospective observational study.

To assess the anatomy of the inferior mesenteric artery (IMA) and its branches by reviewing laparoscopic left-sided colorectal cancer surgery videos and comparing them with preoperative three-dimensional computed tomography (3D-CT) angiography, to verify the accuracy of 3D-CT vascular reconstruction techniques. High-definition surgical videos and preoperative imaging data of 200 patients who underwent laparoscopic left-sided colorectal cancer surgery were analysed, and the alignment of the IMA and its branches in relation to the inferior mesenteric vein (IMV) was observed and summarized. The above two methods were used to measure the length of the IMA and its branches. Of 200 patients, 47.0% had the sigmoid arteries (SAs) arise from the common trunk with the superior rectal artery (SRA), and 30.5% had the SAs arise from the common trunk with the left colic artery (LCA). In 3.5% of patients, the SAs arising from both the LCA and SRA. The LCA, SA, and SRA emanated from the same point in 13.5% of patients, and the LCA was absent in 5.5% of patients. The range of D cm (IMA length measured by intraoperative silk thread) and d cm (IMA length measured by 3D-CT vascular reconstruction) in all cases was 1.84-6.62 cm and 1.85-6.52 cm, respectively, and there was a significant difference between them. (p < 0.001). The lengths between the intersection of the LCA and IMV measured intraoperatively were 0.64-4.29 cm, 0.87-4.35 cm, 1.32-4.28 cm and 1.65-3.69 cm in types 1A, 1B, 1C, and 2, respectively, and there was no significant difference between the groups (p = 0.994). There was only a significant difference in the length of the IMA between the 3D-CT vascular reconstruction and intraoperative observation data, which can provide guidance to surgeons in preoperative preparation.

Predictive effect of the systemic inflammation response index (SIRI) on the efficacy and prognosis of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

BACKGROUND: Inflammation is a part of tumours, and inflammatory cells can affect the proliferation, invasion, and development of tumour cells. An increasing number of peripheral blood inflammatory markers have been found to play very important roles in the treatment and prognosis of cancer patients. The systemic inflammatory response index (SIRI) is a newer inflammatory marker, and its role in colorectal cancer, especially in locally advanced rectal cancer, is still unclear. METHODS: From 2015 to 2020, 198 patients with locally advanced rectal cancer (LARC) who underwent surgery following neoadjuvant chemoradiotherapy (Neo-CRT) were analysed. Patients were categorized into good- and poor- response groups according to their pathological results, and clinical characteristics and baseline parameters were compared between the two groups. The optimal cutoff values for inflammatory indicators were determined using receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using the Cox proportional hazard model. Survival analysis was performed via the Kaplan‒Meier method. RESULTS: After patients were grouped into good and poor response groups, indicator differences were found in CEA, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and SIRI. According to the ROC analysis, the NLR (P = 0.015), SII (P = 0.001), and SIRI (P = 0.029) were significant prognostic factors. After univariate and multivariate analyses of the Cox proportional hazards regression model, only the SIRI was found to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Finally, Kaplan‒Meier survival curves also confirmed the ability of the SIRI to predict survival. CONCLUSION: The preoperative SIRI can be used to predict the response to Neo-CRT in LARC patients and is an independent predictor of OS and DFS in postoperative patients. A high SIRI was associated with poor radiotherapy response and predicted poor OS and DFS.

M2 Macrophage-Derived Extracellular Vesicles Containing MicroRNA-501-3p Promote Colon Cancer Progression Through the SETD7/DNMT1/SOCS3 Axis.

BACKGROUND: Macrophage-derived extracellular vesicles with microRNAs can cause and develop colon cancer. OBJECTIVE: To investigate M2 macrophage-derived extracellular vesicles and colon cancer. DESIGN: A prospective and experimental study of M2 macrophage-derived extracellular vesicles in colon cancer. SETTING: This study was completed at the Fourth Hospital of Hebei Medical University. PATIENTS: Patients with colon cancer who had undergone surgical resection. MAIN OUTCOME MEASURES: Suppressor of cytokine signaling 3, miR-501-3p, SET domain containing 7, and DNA methyltransferase 1 were measured in colon cancer samples. Multiple experiments determined suppressor of cytokine signaling 3, miR-501-3p, SET domain containing 7, and DNA methyltransferase 1 binding affinity. M2 macrophages were cultivated from M0 macrophages isolated from peripheral blood mononuclear cells of a healthy donor and polarized to produce extracellular vesicles. Gain- or loss-of-function tests using colon cancer cells and M2 macrophage-derived extracellular vesicles revealed cell biological processes. Finally, animal models were created to test how miR-501-3p from M2-extracellular vesicles affects tumor growth via the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3. RESULTS: Colon cancer increased miR-501-3p and DNA methyltransferase 1 and downregulated suppressor of cytokine signaling 3 and SET domain containing 7. miR-151-3p inhibited SET domain containing 7, upregulating DNA methyltransferase 1. Increased promoter methylation by DNA methyltransferase 1 decreased suppressor of cytokine signaling 3 expression. M2-EVs with miR-501-3p regulated the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to induce apoptosis and colon cancer cell growth, invasion, and migration. M2-EV-delivered miR-501-3p also regulated the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to promote tumor growth in animals. LIMITATIONS: Further research is needed in clinical application of M2 macrophage-derived extracellular vesicles containing miR-501-3p as a biomarker of colon cancer. CONCLUSIONS: M2 macrophage-derived extracellular vesicles with miR-501-3p regulate the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to promote colon cancer. LAS VESCULAS EXTRACELULARES DERIVADAS DE MACRFAGOS M QUE CONTIENEN MICROARNP PROMUEVEN LA PROGRESIN DEL CNCER DE COLON A TRAVS DEL EJE SETD/DNMT/SOCS: ANTECEDENTES:Las vesículas extracelulares derivadas de macrófagos con microARN pueden causar y desarrollar cáncer de colon.OBJETIVO:Investigamos las vesículas extracelulares derivadas de macrófagos M2 y el cáncer de colon.DISEÑO:Un estudio prospectivo y experimental de vesículas extracelulares derivadas de macrófagos M2 en el cáncer de colon.ESCENARIO:Este estudio se completó en el Cuarto Hospital de la Universidad Médica de Hebei.PACIENTES:Pacientes con cáncer de colon sometidos a resección quirúrgica.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron el supresor de la señalización de citoquinas 3, miR-501-3p, SETD7 y la ADN metiltransferasa 1 en muestras de cáncer de colon. Múltiples experimentos determinaron la afinidad de unión del supresor de la señalización de citoquinas 3, de miR-501-3p, de SETD7 y de la ADN metiltransferasa 1. Los macrófagos M2 se cultivaron a partir de macrófagos M0 aislados de células mononucleares de sangre periférica de donantes sanos y se polarizaron para producir vesículas extracelulares. Las pruebas de ganancia o pérdida de función utilizando células de cáncer de colon y vesículas extracelulares derivadas de macrófagos M2 revelaron procesos biológicos celulares. Finalmente, se crearon modelos animales para probar cómo miR-501-3p de vesículas extracelulares M2 afecta el crecimiento tumoral a través del SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3.RESULTADOS:El cáncer de colon aumentó el miR-501-3p y la ADN metiltransferasa 1 y reguló negativamente el supresor de la señalización de citoquinas 3 y SETD7. miR-151-3p inhibió SETD7, regulando positivamente la ADN metiltransferasa 1. El aumento de la metilación del promotor por la ADN metiltransferasa 1 produjo disminución de la expresión del supresor de señalización de citocinas 3. Los M2-EV con miR-501-3p regularon el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para inducir apoptosis y crecimiento, invasión y migración de células de cáncer de colon. El miR-501-3p administrado por M2-EV también reguló el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para promover el crecimiento tumoral en animales.LIMITACIONES:Se necesita más investigación en la aplicación clínica de vesículas extracelulares derivadas de macrófagos M2 que contienen miR-501-3p como biomarcador de cáncer de colon.CONCLUSIONES:Las vesículas extracelulares derivadas de macrófagos M2 con miR-501-3p regulan el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para promover el cáncer de colon. (Traducción-Dr. Felipe Bellolio ).

A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer.

The objective of this study is to explore the effects of thymalfasin for injection on perioperative immune function and long-term prognosis of patients with colorectal cancer (CRC). In total, 400 patients who entered the groups from February 2019 to January 2021 and underwent radical resection of CRC in the Fourth Hospital of Hebei Medical University were the study subjects. They were separated into experimental group (0-199, XELOX chemotherapy and thymalfasin for injection) and control group (200-400, XELOX chemotherapy) by random number table, and the experimental group was randomly divided into conventional-dose group (n = 100, 1.6 mg of thymalfasin for injection, twice a week) and high-dose group (n = 100, 1.6 mg of thymalfasin for injection, thrice a week) according to a ratio of 1:1, to analyze the effects of different treatment schemes on perioperative immune function and long-term prognosis of CRC patients. Compared with control group, the conventional-dose group and high-dose group had notably lower incidences of perioperative infection (P < 0.05), with no significant difference in both groups (P > 0.05). The experimental group had significantly lower overall incidence of early and late postoperative complications, local recurrence rate and the incidence of distant metastasis, and higher perioperative immune function indexes and median disease free survival (DFS) (P < 0.05). The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment for such patients, which can benefit patients.

SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis.

Gastric cancer (GC) is a common cancer worldwide with high mortality. Sirtuin 1 (SIRT1) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) are abnormally expressed in GC cells and related to p53, which is involved in ferroptosis. Thus, we explore the mechanism via which SIRT1, APE1, and p53 impact ferroptosis in GC cells. Specifically, GC cells were transfected with small-interfering RNA for SIRT1 (SiSIRT1) or small-interfering RNA for APE1 (SiAPE1) or with short-hairpin RNA for p53, and the cell viability, Fe2+, malondialdehyde (MDA), and glutathione (GSH) contents were detected by cell counting kit-8 assay and enzyme-linked immunosorbent assay. Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were conducted to quantify SIRT1, APE1, p53, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) levels in GC cells. Silencing of SIRT1 decreased viability, GSH content, and expressions of GPX4 and SLC7A11, while increased Fe2+, MDA content, and p53 expression in GC cells. Such aforementioned effects were reversed by APE1 overexpression. Also, SiAPE1 generated the same effects as SiSIRT1 on the above aspects, which was offset by p53 silencing. In short, SIRT1/APE1 promotes the growth of GC cells by targeting p53 to inhibit ferroptosis.

Correlation Analysis Model of Social Capital and Innovation Performance Based on Knowledge Mapping.

In this paper, the correlation between social capital and innovation performance is analyzed using a knowledge graph approach, and a correlation analysis model is designed for practical use. Given the advantages of knowledge graph technology and the fact that most recommendation models fail to make full use of the correlation between knowledge graph and recommended items, this paper proposes a cross-attention fusion-based knowledge graph recommendation algorithm (CAKR). The CAKR model contains a cross-fusion module, a recommendation task module, and a knowledge graph embedding task module, and the inputs of the two task modules are alternately learned in a low-dimensional space by the cross-fusion module. The input of the two task modules is alternately learned in the low-dimensional space by the cross-fusion module to interact with the two embedding vectors of items and entities, and then, the obtained feature vectors are fed into the relevant task modules, respectively, and then, the results are calculated by the respective prediction functions. There is a mediating role of knowledge management capabilities in the innovation ecology perspective between social capital and innovation performance of SMEs. Among them, it fully mediates the relationship dimension of technical social capital, the cognitive dimension of institutional social capital, the relationship and cognitive dimension of market-based social capital, and innovation performance, and partially mediates the structural and cognitive dimension of technical social capital, the structural and relationship dimension of institutional social capital, and innovation performance. The relationship between knowledge management capability and innovation performance is positively mediated by environmental dynamics in the innovation ecology perspective, and the positive effect of knowledge management capability on innovation performance is more significant when the environmental dynamics are stronger, and vice versa. Finally, based on the results of the empirical study, some management suggestions are provided on how SMEs can reasonably utilize social capital to enhance their innovation performance.

Plasminogen activator, urokinase enhances the migration, invasion, and proliferation of colorectal cancer cells by activating the Src/ERK pathway.

Background: This paper aims to explore the effects of plasminogen activator, urokinase (PLAU) expression on the migration, invasion, and proliferation of colorectal cancer (CRC) cells and to preliminarily analyze its possible mechanism, thereby laying a foundation for the research on potential biological targets of CRC. Methods: CRC-related mRNA was screened in Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/gds/). Differentially expressed genes (DEGs) were obtained for functional enrichment analysis. The enriched pathway and key involved functional gene were screened for further in vitro and in vivo analysis CRC cells were transfected with PLAU-NC (negative control), PLAU-mimic, and PLAU-inhibitor for 48 h and divided into the above groups for later studies. The migration, invasion, and proliferation capacities of CRC cells were detected using wound healing, Transwell, and colony formation assays, respectively. The Src inhibitor saracatinib (AZD0530) was added to the PLAU-NC and PLAU-mimic groups, and the expression levels of Src/extracellular signal-regulated kinase (ERK) pathway-, migration-, invasion-, and proliferation-related proteins were detected by Western blotting. Results: The results showed that after upregulation of PLAU, the number of CRC cells (SW480) that migrated to the center of the wound significantly increased, the number of cells that migrated and invaded through the basement membrane increased in the PLAU-mimic group, and the number of colonies also increased. These results suggest that increasing PLAU expression promotes the migration, invasion, and proliferation of CRC cells. At the same time, the molecular mechanism of PLAU in CRC cells was investigated by downregulating the protein expression of Src combined with the results of the bioinformatics analysis. Western blotting revealed that the protein expressions of phosphorylated Src (p-Src) and phosphorylated ERK (p-ERK) in SW480 and SW620 cells increased significantly in the PLAU-mimic group compared with the PLAU-NC group, while the results were the opposite in the PLAU-inhibitor group. After being treated with saracatinib, we observed significantly decreased protein levels of p-ERK, matrix metallopeptidase 2 (MMP-2), MMP-3, MMP-9, Cyclin D1, and Cyclin A2 in the SW480 cells. Conclusions: In conclusion, PLAU affects the migration, invasion, and proliferation of CRC cells by activating the Src/ERK pathway.