Clinical, Pathological and Immunohistochemical Characteristics of Patients with Primary Testicular Lymphoma Undergoing Orchiectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Primary testicular lymphoma (PTL) is a rare and aggressive malignant tumour with no specific clinical symptoms. Large-scale evidence-based medical evidence to guide preoperative diagnosis is lacking at present. This study aimed to analyse the clinical, pathological and immunohistochemical characteristics of patients with PTL undergoing testicular resection surgery. METHODS: Literature on the clinical characteristics of patients with PTL undergoing orchiectomy was retrieved from databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data. The search covered all available records from the inception of these databases until December 31, 2023. Data extraction was followed by a meta-analysis using Stata 15.0 software. RESULTS: A total of 22 articles and 475 cases of PTL were included. The meta-analysis revealed that 58.1% of patients with PTL undergoing orchiectomy were under 60 years old, and 41.9% were 60 years or older. The lesion is mostly located on the right side (55.1%). Common symptoms included testicular swelling and falling swelling (91.3%), hydrocele testis (31.0%) and testicular pain (23.0%). Ann Arbor stages I-IV accounted for 53.3%, 16.7%, 14.8% and 15.7%, respectively. Diffuse large B-cell lymphoma (DLBCL) cases were higher at 95.5% than NK/T-cell lymphoma cases at 8.2%. Amongst DLBCL cases, 69.3% were non-germinal centre B-cell (GCB) subtype, and 27.6% were GCB subtype. Immunohistochemistry markers showed 95.9% CD3 negative, 94.9% CD10 negative, 94.4% CD20 positive, 88.4% multiple myeloma oncogene-1 (MUM-1) negative, 73.6% B-cell lymphoma-6 (BCL-6) negative and 66.5% BCL-2 positive. Laboratory findings indicated that 70.4% of patients had a tumour proliferating cell nuclear antigen (Ki67) index of ≥80%, 36.0% had increased serum lactate dehydrogenase level and 22.9% had increased serum ß2-microglobulin level. CONCLUSIONS: PTL is rare, and it often occurs in elderly male patients. Common symptoms include testicular swelling and falling swelling, and the common histological type is DLBCL. Diagnosis should be based on histopathological characteristics and immunohistochemical examination.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Shortened Cerebral Circulation Time Predicts Resistance to Obliteration in High-Flow Brain Arteriovenous Malformations After Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: Treatment selection for brain arteriovenous malformations (BAVMs) is complicated by BAVM size, location, and hemodynamics. Quantitative digital subtraction angiography is used to quantify the hemodynamic impact of BAVMs on cerebral circulation. This study investigated the association between cerebral circulation time and the complete obliteration (CO) rate of BAVMs after stereotactic radiosurgery (SRS). METHODS: We analyzed the data of 143 patients who underwent SRS for BAVMs between January 2011 and December 2019 in our institute. Their pre-SRS magnetic resonance imaging and angiography images were analyzed to acquire BAVM characteristics and quantitative digital subtraction angiography parameters. Modified cerebral circulation time (mCCT) was defined as the time difference between the bolus arrival time of the ipsilateral cavernous internal carotid artery and that of the parietal vein, as determined from the lateral view of images obtained using digital subtraction angiography. Cox regression with hazard ratios and Kaplan-Meier analyses were conducted to determine the associations between the parameters and BAVM CO after SRS. RESULTS: Of the 143 patients, 101 (70.6%) achieved BAVM CO. According to the multivariate analyses, an increased mCCT (hazard ratio: 1.24, P = .041) was the independent factor associated with BAVM CO after adjustment for age, sex, hemorrhagic presentation, a BAVM volume of >5 cm3, and a margin dose of >18 Gy. Individuals with an mCCT of ≤2.32 s had a lower 36-month probability of BAVM CO than did those with an mCCT of >2.32 s (44.1% ± 6.8% vs 63.3% ± 5.6%, P = .034). CONCLUSION: The hemodynamic impact of high-flow BAVM demonstrated by a shortened mCCT is associated with a lower BAVM CO rate after SRS.

Del Nido cardioplegia versus cold blood cardioplegia in adult cardiac surgery: a meta-analysis of randomized clinical trials.

OBJECTIVE: Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery. METHODS: We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model. RESULTS: A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable. CONCLUSION: Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.

Bifidobacterium animalis subsp. lactis LPL-RH improves postoperative gastrointestinal symptoms and nutrition indexes by regulating the gut microbiota in patients with valvular heart disease: a randomized controlled trial.

Gastrointestinal symptoms constitute a frequent complication in postoperative patients with valvular heart disease (VHD), impacting their postoperative recovery. Probiotics contribute to regulating human gut microbiota balance and alleviating postoperative gastrointestinal symptoms. Our objective involved assessing the potential of Bifidobacterium animalis subsp. lactis LPL-RH to alleviate postoperative gastrointestinal symptoms and expedite patient recovery. Adult patients diagnosed with VHD scheduled for valve surgery were enrolled. 110 patients were randomly divided into two groups and received LPL-RH or a placebo for 14 days. Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptoms Questionnaire. An analysis of the time to recovery of bowel function and various postoperative variables was conducted in both study groups. Variations in the intestinal microbiota were detected via 16S rRNA sequencing. The study was completed by 105 participants, with 53 in the probiotic group and 52 in the placebo group. Compared to the placebo group, LPL-RH significantly reduced the total gastrointestinal symptom score after surgery (p = 0.004). Additionally, LPL-RH was found to significantly reduce abdominal pain (p = 0.001), bloating (p = 0.018), and constipation (p = 0.022) symptom scores. Furthermore, LPL-RH dramatically shortened the time to recovery of bowel function (p = 0.017). Moreover, LPL-RH administration significantly enhanced patients' postoperative nutrition indexes (red blood cell counts, hemoglobin level, p < 0.05). Microbiome analysis showed that the composition and diversity of the postoperative intestinal microbiota differed between the probiotic and placebo groups. No adverse incidents associated with probiotics were documented, emphasizing their safety. This study initially discovered that oral B. animalis subsp. lactis LPL-RH can assist in regulating intestinal microbiota balance, alleviating gastrointestinal symptoms, promoting intestinal function recovery, and enhancing nutrition indexes in patients with VHD after surgery. Regulating the intestinal microbiota may represent a potential mechanism for LPL-RH to exert clinical benefits.

A novel fully automatic segmentation and counting system for metastatic lymph nodes on multimodal magnetic resonance imaging: Evaluation and prognostic implications in nasopharyngeal carcinoma.

BACKGROUND: The number of metastatic lymph nodes (MLNs) is crucial for the survival of nasopharyngeal carcinoma (NPC), but manual counting is laborious. This study aims to explore the feasibility and prognostic value of automatic MLNs segmentation and counting. METHODS: We retrospectively enrolled 980 newly diagnosed patients in the primary cohort and 224 patients from two external cohorts. We utilized the nnUnet model for automatic MLNs segmentation on multimodal magnetic resonance imaging. MLNs counting methods, including manual delineation-assisted counting (MDAC) and fully automatic lymph node counting system (AMLNC), were compared with manual evaluation (Gold standard). RESULTS: In the internal validation group, the MLNs segmentation results showed acceptable agreement with manual delineation, with a mean Dice coefficient of 0.771. The consistency among three counting methods was as follows 0.778 (Gold vs. AMLNC), 0.638 (Gold vs. MDAC), and 0.739 (AMLNC vs. MDAC). MLNs numbers were categorized into three-category variable (1-4, 5-9, > 9) and two-category variable (<4, ≥ 4) based on the gold standard and AMLNC. These categorical variables demonstrated acceptable discriminating abilities for 5-year overall survival (OS), progression-free, and distant metastasis-free survival. Compared with base prediction model, the model incorporating two-category AMLNC-counting numbers showed improved C-indexes for 5-year OS prediction (0.658 vs. 0.675, P = 0.045). All results have been successfully validated in the external cohort. CONCLUSIONS: The AMLNC system offers a time- and labor-saving approach for fully automatic MLNs segmentation and counting in NPC. MLNs counting using AMLNC demonstrated non-inferior performance in survival discrimination compared to manual detection.

Radiomics-based lymph nodes prognostic models from three MRI regions in nasopharyngeal carcinoma.

Accurate prediction of the prognosis of nasopharyngeal carcinoma (NPC) is important for treatment. Lymph nodes metastasis is an important predictor for distant failure and regional recurrence in patients with NPC. Traditionally, subjective radiological evaluation increases concerns regarding the accuracy and consistency of predictions. Radiomics is an objective and quantitative evaluation algorithm for medical images. This retrospective analysis was conducted based on the data of 729 patients newly diagnosed with NPC without distant metastases to evaluate the performance of radiomics pretreatment using magnetic resonance imaging (MRI)-determined metastatic lymph nodes models to predict NPC prognosis with three delineation methods. Radiomics features were extracted from all lymph nodes (ALN), largest lymph node (LLN), and largest slice of the largest lymph node (LSLN) to generate three radiomics signatures. The radiomics signatures, clinical model, and radiomics-clinic merged models were developed in training cohort for predicting overall survival (OS). The results showed that LSLN signature with clinical factors predicted OS with high accuracy and robustness using pretreatment MR-determined metastatic lymph nodes (C-index [95 % confidence interval]: 0.762[0.760-0.763]), providing a new tool for treatment planning in NPC.

Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.

Gastrodin ameliorates synaptic impairment, mitochondrial dysfunction and oxidative stress in N2a/APP cells.

Alzheimer's disease is characterized by abnormal ß-amyloid and tau accumulation, mitochondrial dysfunction, oxidative stress, and synaptic dysfunction. Here, we aimed to assess the mechanisms and signalling pathways in the neuroprotective effect of gastrodin, a phenolic glycoside, on murine neuroblastoma N2a cells expressing human Swedish mutant APP (N2a/APP). We found that gastrodin increased the levels of presynaptic-SNAP, synaptophysin, and postsynaptic-PSD95 and reduced phospho-tau Ser396, APP and Aß1-42 levels in N2a/APP cells. Gastrodin treatment reduced reactive oxygen species generation, lipid peroxidation, mitochondrial fragmentation and DNA oxidation; restored mitochondrial membrane potential and intracellular ATP production. Upregulated phospho-GSK-3ß and reduced phospho-ERK and phospho-JNK were involved in the protective effect of gastrodin. In conclusion, we demonstrated the neuroprotective effect of gastrodin in the N2a/APP cell line by ameliorating the impairment on synaptic and mitochondrial function, reducing tau phosphorylation, Aß1-42 levels as well as reactive oxygen species generation. These results provide new mechanistic insights into the potential effect of gastrodin in the treatment of Alzheimer's disease.

Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

The mechanisms of MicroRNA 21 in premature ovarian insufficiency mice with mesenchymal stem cells transplantation : The involved molecular and immunological mechanisms.

Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.

Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway.

Glioma is the most common type of primary intracranial malignant tumor, and because of its high invasiveness and recurrence, its prognosis remains poor. The present study investigated the biological function of piggyBac transportable element derived 5 (PGBD5) in glioma. Glioma and para-cancerous tissues were obtained from five patients. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of PGBD5. Transwell assay and flow cytometry were used to evaluate cell migration, invasion, apoptosis and cell cycle distribution. In addition, a nude mouse tumor transplantation model was established to study the downstream pathways of PGBD5 and the molecular mechanism was analyzed using transcriptome sequencing. The mRNA and protein expression levels of PGBD5 were increased in glioma tissues and cells. Notably, knockdown of PGBD5 in vitro could inhibit the migration and invasion of glioma cells. In addition, the knockdown of PGBD5 expression promoted apoptosis and caused cell cycle arrest in the G2/M phase, thus inhibiting cell proliferation. Furthermore, in vivo experiments revealed that knockdown of PGBD5 expression could inhibit Ki67 expression and slow tumor growth. Changes in PGBD5 expression were also shown to be closely related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In conclusion, interference with PGBD5 could inhibit the malignant progression of glioma through the PPAR pathway, suggesting that PGBD5 may be a potential molecular target of glioma.

Preclinical evaluation of AGTR1-Targeting molecular probe for colorectal cancer imaging in orthotopic and liver metastasis mouse models.

Despite advancements in colorectal cancer (CRC) treatment, the prognosis remains unfavorable for patients with distant liver metastasis. Fluorescence molecular imaging with specific probes is increasingly used to guide CRC surgical resection in real-time and treatment planning. Here, we demonstrate the targeted imaging capacity of an MPA-PEG4-N3-Ang II probe labeled with near-infrared (NIR) fluorescent dye targeting the angiotensin II (Ang II) type 1 receptor (AGTR1) that is significantly upregulated in CRC. MPA-PEG4-N3-Ang II was highly selective and specific to in vitro tumor cells and in vivo tumors in a mouse CRC xenograft model. The favorable ex vivo imaging and in vivo biodistribution of MPA-PEG4-N3-Ang II afforded tumor-specific accumulation with low background and >10 contrast tumor-to-colorectal values in multiple subcutaneous CRC models at 8 h following injection. Biodistribution analysis confirmed the probe's high uptake in HT29 and HCT116 orthotopic and liver metastatic models of CRC with signal-to-noise ratio (SNR) values of tumor-to-colorectal and -liver fluorescence of 5.8 ± 0.6, 5.3 ± 0.7, and 2.7 ± 0.5, 2.6 ± 0.5, respectively, enabling high-contrast intraoperative tumor visualization for surgical navigation. Given its rapid tumor targeting, precise tumor boundary delineation, durable tumor retention and docking study, MPA-PEG4-N3-Ang II is a promising high-contrast imaging agent for the clinical detection of CRC.

Optimal cut-off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy.

BACKGROUND: We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). METHODS: According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan-Meier curves and log-rank tests. RESULTS: Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. CONCLUSIONS: With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

A review for the impacts of circadian disturbance on urological cancers.

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

Exosomal MALAT1 promotes the proliferation of esophageal squamous cell carcinoma through glyoxalase 1-dependent methylglyoxal removal.

In previous study we characterized the oncogenic role of long non-coding RNA MALAT1 in esophageal squamous cell carcinoma (ESCC), but the detailed mechanism remains obscure. Here we identified glyoxalase 1 (GLO1) as the most possible executor of MALAT1 by microarray screening. GLO1 is responsible for degradation of cytotoxic methylglyoxal (MGO), which is by-product of tumor glycolysis. Accumulated MGO may lead to glycation of DNA and protein, resulting in elevated advanced glycation end products (AGEs), while glyoxalase 1 detoxify MGO to alleviate its cytotoxic effect to tumor cells. GLO1 interfering led to accumulation of AGEs and following activation of DNA injury biomarkers, which lead to cell cycle arrest and growth inhibition. In silico analysis based on online database revealed abundant enrichment of histone acetylation marker H3K27ac in GLO1 promotor, and acetyltransferase inhibitor C646 declined GLO1 expression. Acetyltransferase KAT2B, which was also identified as a target of MALAT, mediated histone lysine acetylation of GLO1 promotor, which was confirmed by ChIP-qPCR experiment. Shared binding sites of miR-206 were found on MALAT1 and KAT2B mRNA. Dual-luciferase reporter assays confirmed interaction within MALAT1-miR-206-GLO1. Finally, we identified MALAT1 encapsuled by exosome from donor cells, and transferred malignant behaviors to recipient cells. The secreted exosomes may enter circulation, and serum MALAT1 level combined with traditional tumor markers showed potential power for ESCC diagnosis.

Cuproptosis-related ceRNA axis triggers cell proliferation and cell cycle through CBX2 in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Despite substantial advances in treatment, the prognosis of patients with LUAD remains unfavorable. The ceRNA axis has been reported to play an important role in the pathogenesis of LUAD. In addition, cuproptosis is considered an important factor in tumorigenesis. The expression of CBX2 has been associated with the development of multiple tumors, including LUAD. However, the precise molecular mechanisms through which the cuproptosis-related ceRNA network regulates CBX2 remain unclear. METHODS: The DEGs between tumor and normal samples of LUAD were identified in TCGA database. The "ConsensusClusterPlus" R package was used to perform consensus clustering based on the mRNA expression matrix and cuproptosis-related gene expression profile. Then, LASSO-COX regression analysis was performed to identify potential prognostic biomarkers associated with cuproptosis, and the ceRNA network was constructed. Finally, the mechanisms of ceRNA in LUAD was studied by cell experiments. RESULTS: In this study, the AC144450.1/miR-424-5p axis was found to promote the progression of LUAD by acting on CBX2. The expression of AC144450.1 and miR-424-5p can be altered to regulate CBX2 and is correlated with cell proliferation and cell cycle of LUAD. Mechanistically, AC144450.1 affects the expression of CBX2 by acting as the ceRNA of miR-424-5p. In addition, a cuproptosis-related model were constructed in this study to predict the prognosis of LUAD. CONCLUSIONS: This study is the first to demonstrate that the AC144450.1/miR-424-5p/CBX2 axis is involved in LUAD progression and may serve as a novel target for its diagnosis and treatment.

LD-UNet: A long-distance perceptual model for segmentation of blurred boundaries in medical images.

The blurriness of boundaries in medical image target regions hinders further improvement in automatic segmentation accuracy and is a challenging problem. To address this issue, we propose a model called long-distance perceptual UNet (LD-UNet), which has a powerful long-|distance perception ability and can effectively perceive the semantic context of an entire image. Specifically, LD-UNet utilizes global and local long-distance induction modules, which endow the model with contextual semantic induction capabilities for long-distance feature dependencies. The modules perform long-distance semantic perception at the high and low stages of LD-UNet, respectively, effectively improving the accuracy of local blurred information assessment. We also propose a top-down deep supervision method to enhance the ability of the model to fit data. Then, extensive experiments on four types of tumor data with blurred boundaries are conducted. The dataset includes nasopharyngeal carcinoma, esophageal carcinoma, pancreatic carcinoma, and colorectal carcinoma. The dice similarity coefficient scores obtained by LD-UNet on the four datasets are 73.35%, 85.93%, 70.04%, and 82.71%. Experimental results demonstrate that LD-UNet is more effective in improving the segmentation accuracy of blurred boundary regions than other methods with long-distance perception, such as transformers. Among all models, LD-UNet achieves the best performance. By visualizing the feature dependency field of the models, we further explore the advantages of LD-UNet in segmenting blurred boundaries.

Value of radiological depth of invasion in non-pT4 Oral tongue squamous cell carcinoma: implication for preoperative MR T-staging.

OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.