Computational dissection of the regulatory mechanisms of aberrant metabolism in remodeling the microenvironment of breast cancer.

The composition of T cell subsets and tumor-specific T cell interactions within the tumor microenvironment (TME) contribute to the heterogeneity observed in breast cancer. Moreover, aberrant tumor metabolism is often intimately linked to dysregulated anti-tumor immune function of T cells. Identifying key metabolic genes that affect immune cell interactions thus holds promise for uncovering potential therapeutic targets in the treatment of breast cancer. This study leverages single-cell transcriptomic data from breast cancer to investigate tumor-specific T-cell subsets and their interacting subnetworks in the TME during cancer progression. We further assess the metabolic pathway activities of tumor-specifically activated T-cell subsets. The results reveal that metabolic pathways involved in insulin synthesis, secretion, degradation, as well as fructose catabolism, significantly influence multiple T cell interactions. By integrating the metabolic pathways that significantly up-regulate T cells in tumors and influence their interactions, we identify key abnormal metabolic genes associated with T-cell collaboration and further develop a breast cancer risk assessment model. Additionally, using gene expression profiles of prognosis-related genes significantly associated with aberrant metabolism and drug IC50 values, we predict targeted drugs, yielding potential candidates like GSK-J4 and PX-12. This study integrate the analysis of abnormal T-cell interactions and metabolic pathway abnormalities in the breast cancer TME, elucidating their roles in cancer progression and providing leads for novel breast cancer therapeutic strategies.

The Regulatory Role of Myomaker in the Muscle Growth of the Chinese Perch (Siniperca chuatsi).

The fusion of myoblasts is a crucial stage in the growth and development of skeletal muscle. Myomaker is an important myoblast fusion factor that plays a crucial role in regulating myoblast fusion. However, the function of Myomaker in economic fish during posthatching has been poorly studied. In this study, we found that the expression of Myomaker in the fast muscle of Chinese perch (Siniperca chuatsi) was higher than that in other tissues. To determine the function of Myomaker in fast muscle, Myomaker-siRNA was used to knockdown Myomaker in Chinese perch and the effect on muscle growth was determined. The results showed that the growth of Chinese perch was significantly decreased in the Myomaker-siRNA group. Furthermore, both the diameter of muscle fibers and the number of nuclei in single muscle fibers were significantly reduced in the Myomaker-siRNA group, whereas there was no significant difference in the number of BrdU-positive cells (proliferating cells) between the control and the Myomaker-siRNA groups. Together, these findings indicate that Myomaker may regulate growth of fast muscle in Chinese perch juveniles by promoting myoblast fusion rather than proliferation.

Hepatic glomus tumor, a case report and literature review.

Introduction: This case report documents an exceptionally rare hepatic glomus tumor, contributing valuable insights to the diagnosis and differential diagnosis of such tumors. Main symptoms and important clinical findings: A 58-year-old male was admitted in 2023 due to unexplained elevation of bilirubin discovered during routine laboratory tests. The patient denied any symptoms, and physical examination revealed no positive findings. Laboratory tests indicated elevated bilirubin, while serum tumor markers remained within normal ranges. Contrast-enhanced computed tomography revealed an indistinctly bordered hepatic mass, displaying uneven and marked enhancement in the arterial phase and sustained enhancement in the venous phase. The main diagnoses therapeutic interventions and outcomes: The patient underwent laparoscopic partial hepatectomy, and pathological examination suggested a spindle cell tumor of mesenchymal origin. Immunohistochemistry confirmed positive staining for smooth muscle actin, leading to the final diagnosis of a hepatic glomus tumor with undetermined malignant potential. Follow-up at 6 months postoperatively showed no signs of metastasis or recurrence. Conclusion: This case underscores the subtle radiological distinctions of hepatic glomus tumors, resembling hemangiomas but manifesting unique features. Additionally, the crucial role of immunohistochemistry in achieving a definitive diagnosis is emphasized in this report.

Single-nucleus sequencing unveils heterogeneity in renal cell carcinomas microenvironment: Insights into pathogenic origins and treatment-responsive cellular subgroups.

BACKGROUND: Different individuals with renal cell carcinoma (RCC) exhibit substantial heterogeneity in histomorphology, genetic alterations in the proteome, immune cell infiltration patterns, and clinical behavior. OBJECTIVES: This study aims to use single-nucleus sequencing on ten samples (four normal, three clear cell renal cell carcinoma (ccRCC), and three chromophobe renal cell carcinoma (chRCC)) to uncover pathogenic origins and prognostic characteristics in patients with RCC. METHODS: By using two algorithms, inferCNV and k-means, the study explores malignant cells and compares them with the normal group to reveal their origins. Furthermore, we explore the pathogenic factors at the gene level through Summary-data-based Mendelian Randomization and co-localization methods. Based on the relevant malignant markers, a total of 212 machine-learning combinations were compared to develop a prognostic signature with high precision and stability. Finally, the study correlates with clinical data to investigate which cell subtypes may impact patients' prognosis. RESULTS & CONCLUSION: Two main origin tumor cells were identified: Proximal tubule cell B and Intercalated cell type A, which were highly differentiated in epithelial cells, and three gene loci were determined as potential pathogenic genes. The best malignant signature among the 212 prognostic models demonstrated high predictive power in ccRCC: (AUC: 0.920 (1-year), 0.920 (3-year) and 0.930 (5-year) in the training dataset; 0.756 (1-year), 0.828 (3-year), and 0.832 (5-year) in the testing dataset. In addition, we confirmed that LYVE1+ tissue-resident macrophage and TOX+ CD8 significantly impact the prognosis of ccRCC patients, while monocytes play a crucial role in the prognosis of chRCC patients.

Structural identification, rheological properties and immunological receptor of a complex galacturonoglucan from fruits of Schisandra chinensis (Turcz.) Baill.

A complex heteropolysaccharide SCP-2 named schisanan B (Mw = 1.005 × 105 g/mol) was obtained from water extracts of Schisandra chinensis fruits, and its planar structure was finally deduced as a galacturonoglucan by a combination of monosaccharide compositions, methylation analysis, partial acid hydrolysis, enzymatic hydrolysis and 1D/2D-nuclear magnetic resonance spectroscopy. The conformation of SCP-2 exhibited a globular shape with branching in ammonium formate aqueous solutions. The rheological properties of SCP-2 were investigated on concentrations, temperature, pH and salts. The in vitro immunomodulatory activity assay demonstrated that SCP-2 significantly enhanced the production of nitric oxide (NO) and stimulated the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in macrophages. Through a combination of high-resolution live-cell imaging, surface plasmon resonance, and molecular docking techniques, SCP-2 exhibited a strong binding affinity with the Toll-like receptor 4 (TLR4). Moreover, western blot analysis revealed that SCP-2 effectively induced downstream signaling proteins associated with TLR4 activation, thereby promoting macrophage activation. The evidence strongly indicates that TLR4 functions as a membrane protein target in the activation of macrophages and immune regulation induced by SCP-2.

The role of miR-216a-mediated Nrf2 pathway in muscle oxidative stress of Siniperca chuatsi induced by cadmium.

Cadmium (Cd) is a toxic heavy metal pollutant in the environment. Excessive Cd in water has toxic effects on fish, endangering their healthy growth and ultimately affecting the quality and safety of aquatic products. To evaluate the toxicity of excessive Cd to fish through potential oxidative damage, Siniperca chuatsi was exposed to Cd in water for 15 days. It was found that Cd exposure significantly decreased the survival rate of S. chuatsi and Cd was detected in their muscle. Meanwhile, Cd disrupts the redox balance by reducing antioxidant enzyme activities, increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle, and promoting oxidative damage. Histomorphology showed that enlargement of muscle fiber gaps, cell swelling and vacuolar degeneration after Cd exposure. In addition, Cd toxicity induced up-regulating the expression of miR-216a, while down-regulation of Nrf2 protein and its downstream antioxidant enzyme genes expression. Further analysis revealed that miR-216a was significantly negatively correlated with the expression of Nrf2, and injection of miR-216a antagomir significantly enhanced the expression of Nrf2 and antioxidant enzyme genes, as well as the activity of antioxidant enzymes, thereby reducing the damage of Cd to fish. These results suggested that miR-216a-mediated Nrf2 signaling pathway plays an important role in Cd-induced oxidative stress of S. chuatsi muscle.

Non-polypoid Colorectal Lesions Detection and False Positive Detection by Artificial Intelligence under Blue Laser Imaging and Linked Color Imaging.

Objectives: Artificial intelligence (AI) with white light imaging (WLI) is not enough for detecting non-polypoid colorectal polyps and it still has high false positive rate (FPR). We developed AIs using blue laser imaging (BLI) and linked color imaging (LCI) to detect them with specific learning sets (LS). Methods: The contents of LS were as follows, LS (WLI): 1991 WLI images of lesion of 2-10 mm, LS (IEE): 5920 WLI, BLI, and LCI images of non-polypoid and small lesions of 2-20 mm. LS (IEE) was extracted from videos and included both in-focus and out-of-focus images. We designed three AIs as follows: AI (WLI) finetuned by LS (WLI), AI (IEE) finetuned by LS (WLI)+LS (IEE), and AI (HQ) finetuned by LS (WLI)+LS (IEE) only with images in focus. Polyp detection using a test set of WLI, BLI, and LCI videos of 100 non-polypoid or non-reddish lesions of 2-20 mm and FPR using movies of 15 total colonoscopy were analyzed, compared to 2 experts and 2 trainees. Results: The sensitivity for LCI in AI (IEE) (83%) was compared to that for WLI in AI (IEE) (76%: p=0.02), WLI in AI (WLI) (57%: p<0.01), BLI in AI (IEE) (78%: p=0.14), and LCI in trainees (74%: p<0.01). The sensitivity for LCI in AI (IEE) (83%) was significantly higher than that in AI (HQ) (78%: p<0.01). The FPR for LCI (6.5%) in AI (IEE) were significantly lower than that in AI (HQ) (17.3%: p<0.01). Conclusions: AI finetuned by appropriate LS detected non-reddish and non-polypoid polyps under LCI.

Linked Color Imaging with Artificial Intelligence Improves the Detection of Early Gastric Cancer.

INTRODUCTION: Esophagogastroduodenoscopy is the most important tool to detect gastric cancer (GC). In this study, we developed a computer-aided detection (CADe) system to detect GC with white light imaging (WLI) and linked color imaging (LCI) modes and aimed to compare the performance of CADe with that of endoscopists. METHODS: The system was developed based on the deep learning framework from 9,021 images in 385 patients between 2017 and 2020. A total of 116 LCI and WLI videos from 110 patients between 2017 and 2023 were used to evaluate per-case sensitivity and per-frame specificity. RESULTS: The per-case sensitivity and per-frame specificity of CADe with a confidence level of 0.5 in detecting GC were 78.6% and 93.4% for WLI and 94.0% and 93.3% for LCI, respectively (p < 0.001). The per-case sensitivities of nonexpert endoscopists for WLI and LCI were 45.8% and 80.4%, whereas those of expert endoscopists were 66.7% and 90.6%, respectively. Regarding detectability between CADe and endoscopists, the per-case sensitivities for WLI and LCI were 78.6% and 94.0% in CADe, respectively, which were significantly higher than those for LCI in experts (90.6%, p = 0.004) and those for WLI and LCI in nonexperts (45.8% and 80.4%, respectively, p < 0.001); however, no significant difference for WLI was observed between CADe and experts (p = 0.134). CONCLUSIONS: Our CADe system showed significantly better sensitivity in detecting GC when used in LCI compared with WLI mode. Moreover, the sensitivity of CADe using LCI is significantly higher than those of expert endoscopists using LCI to detect GC.

A machine learning-based predictive model for biliary stricture attributable to malignant tumors: a dual-center retrospective study.

Background: Biliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes. Methodology: Through a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People's Hospital affiliated with Jiangsu University and the Second People's Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model's accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model's predictions. Results: RF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor. Conclusion: The model's effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

Oleanolic acid derivative self-assembled aggregates based on heparin and chitosan for breast cancer therapy.

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (-35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Electrochemiluminescence of Ultrasmall Silica Nanoparticles from Size Modulation and Multipath Surface State Adjustment for Ultrasensitive HIV-DNA Fragment Detection.

Here, ultrasmall SiO2 nanoparticles (u-SiO2 NPs, <5 nm) with obvious electrochemiluminescence (ECL) phenomenon, which was absent for conventional silica nanoparticles (c-SiO2 NPs), were reported. In a finite ultrasmall volume, the u-SiO2 NPs exhibited increasing ground state energy and higher optical absorption strength due to the electron-hole confinement model and favored catalyzing the reaction through the rapid diffusion of bulk charge, resulting in apparent ECL emission. Then, Zn2+-induced u-SiO2 nanoaggregates (Zn/u-SiO2-Ov nAGG) were synthesized and exhibited improved ECL performance via multipath surface state adjustment of u-SiO2 from several aspects, including aggregation-induced ECL, the generation of oxygen vacancy (Ov), and more positive surface charge. In addition, an ECL biosensor was constructed for ultrasensitive human immunodeficiency virus-related deoxyribonucleic acid detection from 100 aM to 1 nM with a low limit of 50.48 aM, combining the ECL luminescence of Zn/u-SiO2-Ov nAGG with three-dimensional DNA nanomachine-mediated multioutput amplification for enhanced accuracy and sensitivity compared to the single-output method. Therefore, exploring the ECL of ultrasmall nanoparticles via the adjustment of size and surface state provided a valuable indication to a wider investigation and application of novel ECL materials for clinical diagnostic.

Integrative Pan-Cancer Analysis Reveals the Oncogenic Role of MND1 and Validation of MND1's Role in Breast Cancer.

Purpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored. Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays. Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3. Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.

A combined AIMD and DFT study of the low-energy radiation responses of GaN.

Although GaN is a promising candidate for semiconductor devices, degradation of GaN-based device performance may occur when the device is bombarded by high-energy charged particles during its application in aerospace, astronomy, and nuclear-related areas. It is thus of great significance to explore the influence of irradiation on the microstructure and electronic properties of GaN and to reveal the internal relationship between the damage mechanisms and physical characteristics. Using a combined density functional theory (DFT) and ab initio molecular dynamics (AIMD) study, we explored the low-energy recoil events in GaN and the effects of point defects on GaN. The threshold displacement energies (Eds) significantly depend on the recoil directions and the primary knock-on atoms. Moreover, the Ed values for nitrogen atoms are smaller than those for gallium atoms, indicating that the displacement of nitrogen dominates under electron irradiation and the created defects are mainly nitrogen vacancies and interstitials. The formation energy of nitrogen vacancies and interstitials is smaller than that for gallium vacancies and interstitials, which is consistent with the AIMD results. Although the created defects improve the elastic compliance of GaN, these radiation damage states deteriorate its ability to resist external compression. Meanwhile, these point defects lead the Debye temperature to decrease and thus increase the thermal expansion coefficients of GaN. As for the electronic properties of defective GaN, the point defects have various effects, i.e., VN (N vacancy), Gaint (Ga interstitial), Nint (N interstitial), and GaN (Ga occupying the N lattice site) defects induce the metallicity, and NGa (N occupying the Ga lattice site) defects decrease the band gap. The presented results provide underlying mechanisms for defect generation in GaN, and advance the fundamental understanding of the radiation resistances of semiconductor materials.

LINC01535 promotes hepatocellular carcinoma proliferation and metastasis by regulating the miR-214-3p/VASP axis.

Background: Emerging evidence has indicated that long noncoding RNAs (lncRNAs) are associated with the development and progression of several carcinomas, including hepatocellular carcinoma (HCC). However, the role of LINC01535 in HCC is still unknown. Materials and methods: In this study, RNA-seq, CCK-8, colony formation, wound healing, Transwell and tumor xenograft assays were used to explore the function of LINC01535 in the proliferation and metastasis of HCC in vitro and in vivo. Fluorescence in situ hybridization (FISH) assay, bioinformatics analysis, dual-luciferase assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis were used to reveal the interactions of LINC01535, miR-214-3p and VASP. Results: LINC01535 was overexpressed in HCC tissues and HCC cell lines. Gain- and loss-of-function studies revealed that LINC01535 could promote HCC cell proliferation, migration and invasion both in vitro and in vivo. In addition, upregulation of LINC01535 significantly decreased the expression of microRNA-214-3p (miR-214-3p), which was found closely associated with suppressing tumor progression. Moreover, VASP was identified as a direct downstream target gene of miR-214-3p. LINC01535 positively regulated VASP expression by sponging miR-214-3p, and VASP overexpression activated the PI3K/AKT signaling pathway and stimulated epithelial-to-mesenchymal transition (EMT) in HCC. Conclusions: Our study first found that LINC01535 promoted HCC progression by regulating its downstream target, the miR-214-3p/VASP axis, via the PI3K/AKT signaling pathway. The function and novel regulatory mechanism of LINC01535 may provide a valuable target for the diagnosis and treatment of HCC patients.

Comparison of efficacy and safety between robotic-assisted versus laparoscopic surgery for locally advanced mid-low rectal cancer following neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: To some extent, robotic technique does offer certain benefits in rectal cancer surgery than laparoscopic one, while remains a topic of ongoing debate for rectal cancer patients who had undergone neoadjuvant chemoradiotherapy (NCRT). METHODS: Potential studies published until January 2024 were obtained from Web of Science, Cochrane Library, Embase and PubMed. Dichotomous and continuous variables were expressed as odds ratios (ORs) and weighted mean differences (WMDs) with 95% their confidence intervals (CIs), respectively. A random effects model was used if I2 statistic >50%, otherwise a fixed effects model. RESULTS: Eleven studies involving 1079 patients were analyzed. The robotic-assisted group had an 0.4 cm shorter distance from anal verge (95% CI: -0.680 to -0.114, P=0.006) and 1.94 times higher complete total mesorectal excision (TME) rate (OR=1.936, 95% CI: 1.061 to 3.532, P=0.031). However, the operation time in the robotic-assisted group was 54 minutes longer (95% CI: 20.489 to 87.037, P=0.002) than laparoscopic group. In addition, the robotic-assisted group had a lower open conversion rate (OR=0.324, 95% CI: 0.129 to 0.816, P=0.017) and a shorter length of hospital stay (WMD=-1.127, 95% CI: -2.071 to -0.184, P=0.019). CONCLUSION: Robot-assisted surgery offered several advantages over laparoscopic surgery for locally advanced mid-low rectal cancer following NCRT in terms of resection of lower tumours with improved TME completeness, lower open conversion rate and shorter hospital stay, despite longer operative time.

Development of high-quality artificial intelligence for computer-aided diagnosis in determining subtypes of colorectal cancer.

BACKGROUND AND AIM: There are no previous studies in which computer-aided diagnosis (CAD) diagnosed colorectal cancer (CRC) subtypes correctly. In this study, we developed an original CAD for the diagnosis of CRC subtypes. METHODS: Pretraining for the CAD based on ResNet was performed using ImageNet and five open histopathological pretraining image datasets (HiPreD) containing 3 million images. In addition, sparse attention was introduced to improve the CAD compared to other attention networks. One thousand and seventy-two histopathological images from 29 early CRC cases at Kyoto Prefectural University of Medicine from 2019 to 2022 were collected (857 images for training and validation, 215 images for test). All images were annotated by a qualified histopathologist for segmentation of normal mucosa, adenoma, pure well-differentiated adenocarcinoma (PWDA), and moderately/poorly differentiated adenocarcinoma (MPDA). Diagnostic ability including dice sufficient coefficient (DSC) and diagnostic accuracy were evaluated. RESULTS: Our original CAD, named Colon-seg, with the pretraining of both HiPreD and ImageNET showed a better DSC (88.4%) compared to CAD without both pretraining (76.8%). Regarding the attentional mechanism, Colon-seg with sparse attention showed a better DSC (88.4%) compared to other attentional mechanisms (dual: 79.7%, ECA: 80.7%, shuffle: 84.7%, SK: 86.9%). In addition, the DSC of Colon-seg (88.4%) was better than other types of CADs (TransUNet: 84.7%, MultiResUnet: 86.1%, Unet++: 86.7%). The diagnostic accuracy of Colon-seg for each histopathological type was 94.3% for adenoma, 91.8% for PWDA, and 92.8% for MPDA. CONCLUSION: A deep learning-based CAD for CRC subtype differentiation was developed with pretraining and fine-tuning of abundant histopathological images.

Crosstalk between circBMI1 and miR-338-5p/ID4 inhibits AML progression.

BMI1 Polycomb Ring Finger Proto-Oncogene (BMI1) is involved in the pathogenesis of different cancers, including acute myeloid leukemia (AML). However, the role of the circular RNA of BMI1 (circBMI1) has not been studied. Our study aimed to investigate the role and mechanism of circBMI1 in AML. circBMI1 was significantly decreased in bone marrow mononuclear cells aspirated from patients with AML. Receiver operating characteristic curve analysis showed that circBMI1 could distinguish patients with AML from controls. By overexpressing and knocking down circBMI1 in HL-60 cells, we found that circBMI1 inhibited cell proliferation, promoted apoptosis, and increased chemotherapeutic drug sensitivity in AML. Experiments using severe combined immune-deficient mice and circBMI1 transgenic mice showed that mice with circBMI1 overexpression had lower white blood cell counts, which suggested less severe AML invasion. RNA immunoprecipitation and dual-luciferase reporter assay revealed binding sites among circBMI1, miR-338-5p, and inhibitor of DNA binding 4 (ID4). Rescue experiments proved that circBMI1 inhibited AML progression by binding to miR-338-5p, which affected the expression of ID4. By coculturing exosomes extracted from circBMI1-HL-60 and small interfering circBMI1-HL-60 cells with HL-60 cells, we found that exosomes from circBMI1-HL-60 cells showed tumor suppressive effects, namely inhibiting HL-60 proliferation, promoting apoptosis, and increasing chemotherapeutic drug sensitivity. Exosomes from small interfering circBMI1-HL-60 cells showed the opposite effects. circBMI1 may act as an exosome-dependent tumor inhibitor. circBMI1, a potential biomarker for clinical diagnosis, acts as a tumor suppressor in AML by regulating miR-338-5p/ID4 and might affect the pathogenesis of AML by exosome secretion.

Metabolomics reveals the implication of acetoacetate and ketogenic diet therapy in radioiodine-refractory differentiated thyroid carcinoma.

OBJECTIVE: Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC; RAIR-DTC) have a poor prognosis. The aim of this study was to provide new insights and possibilities for the diagnosis and treatment of RAIR-DTC. METHODS: The metabolomics of 24 RAIR-DTC and 18 non-radioiodine-refractory (NonRAIR) DTC patients samples were analyzed by liquid chromatograph-mass spectrometry. Cellular radioiodine uptake was detected with γ counter. Sodium iodide symporter (NIS) expression and thyroid stimulating hormone receptor (TSHR) were measured by Western blot analysis. CCK8 and colony formation assays were used to measure cellular proliferation. Scratch and transwell assays were performed to assess cell migration and invasion. Annexin V/PI staining was used to detect cell apoptosis. Cell growth in vivo was evaluated by a tumor xenograft model. The acetoacetate (AcAc) level was measured by ELISA. Pathological changes, Ki67, NIS, and TSHR expression were investigated by immunohistochemistry. RESULTS: The metabolite profiles of RAIR could be distinguished from those of NonRAIR, with AcAc significantly lower in RAIR. The significantly different metabolic pathway was ketone body metabolism. AcAc increased NIS and TSHR expression and improved radioiodine uptake. AcAc inhibited cell proliferation, migration, and invasion, and as well promoted cell apoptosis. Ketogenic diet (KD) elevated AcAc levels and significantly suppressed tumor growth, as well as improved NIS and TSHR expression. CONCLUSION: Significant metabolic differences were observed between RAIR and NonRAIR, and ketone body metabolism might play an important role in RAIR-DTC. AcAc improved cellular iodine uptake and had antitumor effects for thyroid carcinoma. KD might be a new therapeutic strategy for RAIR-DTC.