Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn's disease.

The pathogenesis of Crohn's disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti-tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.

Hyperactivation and enhanced cytotoxicity of reduced CD8+ gamma delta T cells in the intestine of patients with Crohn's disease correlates with disease activity.

BACKGROUND AND AIMS: We aimed to investigate the immune characteristics of intestinal CD8+ gamma delta T (CD8+ γδ T) cells in Crohn's disease (CD) and their correlation with disease activity. METHODS: The study cohorts included 21 CD patients and 21 healthy individuals. CD8+ γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis. RESULTS: The study revealed a reduction in intestinal CD8+ γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8+ γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8+ γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR+ CD8+ γδT cell ratio, CD8+ γδT ratio, and CD8+ γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B+ CD8+ γδT cell and Perforin+ CD8+ γδT cell were identified as indicators that distinguish mildly moderately active CD cases. CONCLUSIONS: Intestinal CD8+ γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8+ γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8+ γδ T cells can be used as indicators to assist in diagnosing CD patients.

Clinical value of multi-gene testing in distinguishing benign and malignant thyroid nodules.

BACKGROUND: The newly released 2022 WHO Classification of Neuroendocrine Neoplasms (version 5) and a recent update on thyroid tumor classifications have emphasized genetic testing to an unprecedented level. Fine needle aspiration (FNA) has been widely applied for the preoperative diagnosis of thyroid nodules. However, it is limited mainly to testing for a single gene-BRAFV600E, whereas multi-gene testing data are scarce, especially in the Asian population. This study aimed to explore the clinical value of multi-gene testing in the differential diagnosis of benign and malignant thyroid nodules based on the 2023 Bethesda System for Reporting Thyroid Cytopathology (BSRTC). METHODS: A total of 615 thyroid nodules underwent ultrasound-guided fine-needle aspiration cytology (FNAC) were collected from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. The next-generation sequencing platform was applied for multi-gene testing. A panel of well-recognized commonly mutated genes in thyroid cancer were analyzed, including BRAFV600E, KRAS, NRAS, HRAS, TERT, TP53, PAX8/PPARG, CCDC6/ RET and NCOA4/ RET. RESULTS: Gene mutations were identified in 324 nodules (52.7%), with BRAFV600E being the most prevalent driver gene alteration observed in this cohort (233/324; 79.1%), followed by RAS (77/324, 23.8%). The overall malignancy rate of gene mutations was 89.7% in our cohort, of which the lymph node metastasis rate was 45.3%. The combination of multi-gene testing and cytology resulted in 89.3% sensitivity, 95.2% specificity, 98.9% positive predictive value, 64.5% negative predictive value and 90.3% accuracy, which were significantly higher than those from mere cytology (sensitivity 68.6%, specificity 87.5%, positive predictive value 95.9%, negative predictive value 39.8%, accuracy 72.2%). CONCLUSIONS: Multi-gene testing could substantially enhance the detection rate of malignant thyroid nodules and protect patients with benign nodules from unnecessary surgeries. Multi-gene testing provides a valuable reference for individualized preoperative decision-making, which may serve as a crucial method for postoperative treatment and prognosis assessment.

A study of machine learning models for rapid intraoperative diagnosis of thyroid nodules for clinical practice in China.

BACKGROUND: In China, rapid intraoperative diagnosis of frozen sections of thyroid nodules is used to guide surgery. However, the lack of subspecialty pathologists and delayed diagnoses are challenges in clinical treatment. This study aimed to develop novel diagnostic approaches to increase diagnostic effectiveness. METHODS: Artificial intelligence and machine learning techniques were used to automatically diagnose histopathological slides. AI-based models were trained with annotations and selected as efficientnetV2-b0 from multi-set experiments. RESULTS: On 191 test slides, the proposed method predicted benign and malignant categories with a sensitivity of 72.65%, specificity of 100.0%, and AUC of 86.32%. For the subtype diagnosis, the best AUC was 99.46% for medullary thyroid cancer with an average of 237.6 s per slide. CONCLUSIONS: Within our testing dataset, the proposed method accurately diagnosed the thyroid nodules during surgery.

Mucosal Architectural Change is an Important Feature in Distinguishing Crohn's Disease From Others in Terminal Ileum Ulcer Biopsy.

BACKGROUND: Besides Crohn's disease (CD), there are a variety of other causes that can also lead to ulcerations in the terminal ileum. The purpose of this study was to identify useful diagnostic features for CD when evaluating terminal ileum biopsies in patients with endoscopic finding of ulcers. METHODS: Five hundred and seventy-one patients with endoscopic finding of ulcers were included in this retrospective study. Five main histological features were analysed, which were crypt irregularity, mucosal thickening, villous stromal widening (including villous atrophy), granulomas, and pseudopyloric gland metaplasia. Clinical and pathological features were determined by uni- and multivariable logistic regression. Then another independent cohort of 99 patients was established for verifying this nomogram. RESULTS: The crypt irregularity, mucosal thickening, and villous stromal widening were combined to be considered as one new variable named mucosal architectural change which was an independent variable in diagnosing CD. We found that mucosal architectural change, age <40 years, the presence of granulomas, and the presence of pseudopyloric gland metaplasia were independent factors for the pathological diagnosis of CD. Then nomogram was developed, with receiver operating characteristic (ROC) curve (area under the ROC curve [AUC] = 0.927) in training sets, and ROC curve (AUC = 0.913) in validation sets. CONCLUSIONS: We found mucosal architectural change is very helpful in distinguishing CD from non-CD patients. In the context of small biopsy which may lack full scope of changes, the model developed by combining these key features is valuable in predicting a diagnosis of CD, especially in younger patients (age <40 years).

Understanding endoscopic and clinicopathological features of patients with very early onset inflammatory bowel disease: Results from a decade of study.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AIMS: This study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. METHODS: A retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. RESULTS: A total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. CONCLUSIONS: Endoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.

Identification of immune-related hub genes contributing to the pathogenesis, diagnosis, and remission of ulcerative colitis by integrated bioinformatic analyses.

The inflammatory disease ulcerative colitis (UC) is multifaceted, immune-mediated, chronic, and relapsing, which is considered to be mainly driven by dysregulated mucosal immune response. The remission of the inflammatory response is a marker of mucosal healing, relating to the low risk of hospitalizations, colorectal cancer, and colectomy. In spite of this, it is still unclear what the key immunological mechanism is which contributes to UC. Here, we explored the immune mechanism and related key genes underlying the state of inflammation in UC. Co-expression networks were constructed based on the expression profiles of immune-related genes in GSE179285. Using Weighted Gene Co-expression Network Analysis and Protein-protein interactions analysis, common hub genes were identified in the module of interest. Then, screening of real hub genes, significantly differentially expressing in inflamed UC, was carried out by Differential Expression Genes Analysis of GSE75214, GSE53306, and GSE6731datasets and immunohistochemistry of clinical samples. The diagnosis Capacity of the hub gene was identified by "glm" function in R. The potential key immune-related mechanisms were investigated using functional enrichment analysis and gene set enrichment analysis (GSEA). Bioinformatics tools were used to predict potential upstream transcription factors (TF), including the UCSC genome browser, correlation analyses, and JASPAR browser. The analysis revealed the blue module, consisting of 227 immune-related genes, showed the highest correlation with inflamed UC. And then, forty-three common candidates were distinguished. S100A9 was identified within the key module as a real hub gene with good diagnostic performance. The immune genes in the blue module were markedly enriched in the Cytokine-Cytokine receptor interaction. S100A9 most likely gets involved NOD-like receptor (NLR) signaling pathway. SPI1 showed the strongest likelihood to be the regulator. S100A9 was identified as the real immune-related hub gene for inflamed UC. Both diagnosis and remission may be aided by its high expression in the inflamed UC.

A Combination of Pathological Features Identifies Crohn's Disease in Surgical Bowel Resection Specimens.

BACKGROUND: Diagnosis of Crohn's disease is challenging. This study aims to compare the histological features of Crohn's disease and non-Crohn's disease (other intestinal inflammatory diseases) in surgical specimens to identify a set of histologic features distinguishing Crohn's disease from non-Crohn's disease. METHODS: Patients with Crohn's disease (N = 171) and patients with non-Crohn's disease (N = 215) diagnosed between 2010 and 2015 who had surgical bowel resection were identified. The frequency of histological features in surgical resection specimens was compared between these two groups. RESULTS: Univariate analysis revealed that transmural inflammation, subserosal lymphoid aggregates, fissures or sinus-like structures, granulomas or granuloma-like nodules, abnormalities of the enteric nervous system, and mucosa structure alterations (muscularis mucosa thickening or mucosal atrophy with pseudopyloric gland metaplasia) were more frequent in Crohn's disease than non-Crohn's disease cases (p < 0.001 for all). Some of the above histologic features were further grouped as chronic inflammatory change which includes granulomas or granuloma-like nodules, lymphoid aggregates in the muscularis propria or subserosa, fissures or sinus-like structures, and architectural abnormality which is defined as the presence of abnormal enteric nervous system and/or mucosa structural alterations (muscularis mucosa thickening or mucosal atrophy with pseudopyloric gland metaplasia). A combination of transmural inflammation, chronic inflammatory change, and architectural abnormality had a sensitivity of 92.4% and a specificity of 97.7% for Crohn's disease. CONCLUSIONS: In surgical bowel resection specimens, a combination of transmural inflammation, chronic inflammatory change, and architectural abnormality help diagnose Crohn's disease.

Deep Learning-Based Recognition of Cervical Squamous Interepithelial Lesions.

Cervical squamous intraepithelial lesions (SILs) are precursor lesions of cervical cancer, and their accurate diagnosis enables patients to be treated before malignancy manifests. However, the identification of SILs is usually laborious and has low diagnostic consistency due to the high similarity of pathological SIL images. Although artificial intelligence (AI), especially deep learning algorithms, has drawn a lot of attention for its good performance in cervical cytology tasks, the use of AI for cervical histology is still in its early stages. The feature extraction, representation capabilities, and use of p16 immunohistochemistry (IHC) among existing models are inadequate. Therefore, in this study, we first designed a squamous epithelium segmentation algorithm and assigned the corresponding labels. Second, p16-positive area of IHC slides were extracted with Whole Image Net (WI-Net), followed by mapping the p16-positive area back to the H&E slides and generating a p16-positive mask for training. Finally, the p16-positive areas were inputted into Swin-B and ResNet-50 to classify the SILs. The dataset comprised 6171 patches from 111 patients; patches from 80% of the 90 patients were used for the training set. The accuracy of the Swin-B method for high-grade squamous intraepithelial lesion (HSIL) that we propose was 0.914 [0.889-0.928]. The ResNet-50 model for HSIL achieved an area under the receiver operating characteristic curve (AUC) of 0.935 [0.921-0.946] at the patch level, and the accuracy, sensitivity, and specificity were 0.845, 0.922, and 0.829, respectively. Therefore, our model can accurately identify HSIL, assisting the pathologist in solving actual diagnostic issues and even directing the follow-up treatment of patients.

Comprehensive analysis of microbiota signature across 32 cancer types.

Microbial communities significantly inhabit the human body. Evidence shows the interaction between the human microbiome and host cells plays a central role in multiple physiological processes and organ microenvironments. However, the majority of related studies focus on gut microbiota or specific tissues/organs, and the component signature of intratumor microbiota across various cancer types remains unclear. Here, we systematically analyzed the correlation between intratumor microbial signature with survival outcomes, genomic features, and immune profiles across 32 cancer types based on the public databases of Bacteria in Cancer (BIC) and The Cancer Genome Atlas (TCGA). Results showed the relative abundance of microbial taxa in tumors compared to normal tissues was observed as particularly noticeable. Survival analysis found that specific candidate microbial taxa were correlated with prognosis across various cancers. Then, a microbial-based scoring system (MS), which was composed of 64 candidate prognostic microbes, was established. Further analyses showed significant differences in survival status, genomic function, and immune profiles among the distinct MS subgroups. Taken together, this study reveals the diversity and complexity of microbiomes in tumors. Classifying cancer into different subtypes based on intratumor microbial signatures might reasonably reflect genomic characteristics, immune features, and survival status.

Epithelial Gab1 calibrates RIPK3-dependent necroptosis to prevent intestinal inflammation.

As a hallmark of inflammatory bowel disease (IBD), elevated intestinal epithelial cell (IEC) death compromises the gut barrier, activating the inflammatory response and triggering more IEC death. However, the precise intracellular machinery that prevents IEC death and breaks this vicious feedback cycle remains largely unknown. Here, we report that Grb2-associated binder 1 (Gab1) expression is decreased in patients with IBD and inversely correlated with IBD severity. Gab1 deficiency in IECs accounted for the exacerbated colitis induced by dextran sodium sulfate owing to sensitizing IECs to receptor-interaction protein kinase 3-mediated (RIPK3-mediated) necroptosis, which irreversibly disrupted the homeostasis of the epithelial barrier and promoted intestinal inflammation. Mechanistically, Gab1 negatively regulated necroptosis signaling through inhibiting the formation of RIPK1/RIPK3 complex in response to TNF-α. Importantly, administration of RIPK3 inhibitor revealed a curative effect in epithelial Gab1-deficient mice. Further analysis indicated mice with Gab1 deletion were prone to inflammation-associated colorectal tumorigenesis. Collectively, our study defines a protective role for Gab1 in colitis and colitis-driven colorectal cancer by negatively regulating RIPK3-dependent necroptosis, which may serve as an important target to address necroptosis and intestinal inflammation-related disease.

SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis.

SIPRα on macrophages binds with CD47 to resist proengulfment signals, but how the downstream signal of SIPRα controls tumor-infiltrating macrophages (TIMs) is still poorly clarified. Here, we report that the CD47/signal regulatory protein α (SIRPα) axis requires the deneddylation of tyrosine phosphatase SHP2. Mechanistically, Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) was constitutively neddylated on K358 and K364 sites; thus, its autoinhibited conformation was maintained. In response to CD47-liganded SIRPα, SHP2 was deneddylated by sentrin-specific protease 8 (SENP8), which led to the dephosphorylation of relevant substrates at the phagocytic cup and subsequent inhibition of macrophage phagocytosis. Furthermore, neddylation inactivated myeloid-SHP2 and greatly boosted the efficacy of colorectal cancer (CRC) immunotherapy. Importantly, we observed that supplementation with SHP2 allosteric inhibitors sensitized immune treatment-resistant CRC to immunotherapy. Our results emphasize that the CRC subtype that is unresponsive to immunotherapy relies on SIRPαhiSHP2hiNEDD8lo TIMs and highlight the need to further explore the strategy of SHP2 targeting in CRC therapy.

MAN2A1 predicts prognosis and progression through cancer-related pathways in colorectal cancer.

Background: Colorectal cancer (CRC) is a common malignant tumor leading to poor prognosis and high mortality. Mannosidase alpha class 2A member 1 (MAN2A1) turns to oncogene through fusing Fer tyrosine kinase (FER) and associates with multiple cancer occurrence. In order to determine whether MAN2A1 can promote tumorigenesis and metastasis in CRC, we conducted a series of studies. Methods: We obtained gene expression and clinical data of CRC from The Cancer Genome Atlas (TCGA) databases. RNA raw counts data was merged by Python. Batch processing of univariate Cox regression analysis was performed to preliminary identify the genes associated with prognosis. Differentially expressed genes (DEGs) between lymph node metastasis (LNM) patients and non-LNM patients were identified via edgR in Sangerbox tool. Protein-protein interactive (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Kaplan-Meier (KM) survival of CRC patients was analyzed by Sangerbox tool. Clinicopathologic characteristics of CRC patients were analyzed by SPSS statistics software. Differences in RNA expression levels of genes were validated in our cohort by real-time polymerase chain reaction (RT-PCR). Analyses of Signaling pathways and gene ontology were explored by gene set enrichment analysis (GSEA). Results: We first obtained 4,455 genes associated with the prognosis of CRC, and 998 of these genes were also DEGs in CRC between metastatic CRC tissues and in situ tissues. Therein, MAN2A1 expression was downregulated in LNM CRC compared with CRC in situ, also downregulated in CRC compared with adjacent normal tissues, and high gene expression levels of MAN2A1 was associated with better survival. Conclusions: Our study suggested that MAN2A1 could be a potential biomarker significantly related to prognosis and LNM of CRC patients.

A novel methylated cation channel TRPM4 inhibited colorectal cancer metastasis through Ca2+/Calpain-mediated proteolysis of FAK and suppression of PI3K/Akt/mTOR signaling pathway.

Colorectal cancer (CRC) is an aggressive malignancy with poor prognosis. It is imperative to elucidate the potential molecular mechanisms that regulate CRC cell aggressiveness. In present study, the transient receptor potential melastatin 4 (TRPM4), a calcium-activated nonselective cation channel, is downregulated in CRC as a novel methylated tumor suppressor gene (TSG). The reduced mRNA level of TRPM4 is due to the epigenetic methylation of its promoter CpG island (CGI). Moreover, ectopic expression of TRPM4 inhibited tumor growth and metastasis both in vitro and in vivo. Our experiments also demonstrate that TRPM4 restructures the CRC cytoskeleton and activates the Ca2+-mediated calpain pathway through enhancing calcium influx. The western blot analysis shows that the expression of focal adhesion kinase (FAK), a calpain-mediated proteolytic substrate, is markedly suppressed after ectopic overexpression of TRPM4, besides, Akt (also known as protein kinase B, PKB), phosphatidylinositol 3-kinase (PI3K) as well as its central target mTOR have significantly decreased expression accompanied by elevated E-cadherin and restrained matrix metalloproteinases (MMP2/MMP9) expression. The inhibition of protease calpain effectively relieves the retard of FAK/Akt signals and reverses the migration suppression of TRPM4. Taken together, TRPM4, identified as a novel methylated TSG, employs intracellular Ca2+ signals to activate calpain-mediated cleavage of FAK and impede CRC migration and invasion through modulating the PI3K/Akt/mTOR signaling cascade, providing the first evidence that TRPM4 is likely to be a significant biomarker and potential target for CRC therapy.

A risk model of 10 aging-related genes for predicting survival and immune response in triple-negative breast cancer.

Accumulated studies showed that the clinical significance of aging on the development and malignancy of tumors, while the relationship between aging and the prognosis, immune response in triple-negative breast cancer (TNBC) has not been well clarified. Here, we constructed a risk model of 10 prognostic aging-related genes (ARGs) from METABRIC database. Then, TNBC patients were classified into high- and low-risk groups, the survival diversity, immune response, genomic function, and tumor mutation burden (TMB) between different risk groups were explored in METABRIC, TCGA, and GSE58812 cohorts. Results showed that patients in the high-risk group had poorer survival outcomes compared to their counterparts (all p < 0.05), and the nomogram we established showed reliable prediction ability for survival in TNBC patients. Besides, TNBC patients with high-risk scores had a lower expression of immune checkpoint markers and a lower fraction of activated immune cells. Furthermore, GSEA showed that Notch signaling pathway was significantly enriched in the high-risk group. Thus, a risk model based on the aging-related genes was developed and validated in this study, which may serve as a potential biomarker for prognosis and personalized treatment in TNBCs.

A digital twin auxiliary approach based on adaptive sparse attention network for diesel engine fault diagnosis.

Condition monitoring and fault diagnosis of diesel engines are of great significance for safety production and maintenance cost control. The digital twin method based on data-driven and physical model fusion has attracted more and more attention. However, the existing methods lack deeper integration and optimization facing complex physical systems. Most of the algorithms based on deep learning transform the data into the substitution of the physical model. The lack of interpretability of the deep learning diagnosis model limits its practical application. The attention mechanism is gradually developed to access interpretability. In this study, a digital twin auxiliary approach based on adaptive sparse attention network for diesel engine fault diagnosis is proposed with considering its signal characteristics of strong angle domain correlation and transient non-stationary, in which a new soft threshold filter is designed to draw more attention to multi decentralized local fault information dynamically in real time. Based on this attention mechanism, the distribution of fault information in the original signal can be better visualized to help explain the fault mechanism. The valve failure experiment on a diesel engine test rig is conducted, of which the results show that the proposed adaptive sparse attention mechanism model has better training efficiency and clearer interpretability on the premise of maintaining performance.

Quinone oxidoreductase 1 is overexpressed in gastric cancer and associated with outcome of adjuvant chemotherapy and survival.

BACKGROUND: Quinine oxidoreductase 1 (NQO1) plays a vital role in protecting normal cells against oxidative damage and electrophilic attack. It is highly expressed in many solid tumors, suggesting a role in cancer development and progression. However, the role of NQO1 in gastric cancer and its effect on cancer development and prognosis have not been fully investigated. AIM: To investigate the clinical relevance of NQO1 protein expression in gastric cancer and to explore the potential of NQO1 to serve as a prognostic biomarker and therapeutic target. METHODS: In this retrospective study, gastric cancer specimens of 175 patients who were treated between 1995 and 2011 were subjected to immunohistochemistry analyses for NQO1. The correlation of NQO1 expression with gastric cancer prognosis and clinical and pathological parameters was investigated. RESULTS: NQO1 protein was overexpressed in 59.43% (104/175) of the analyzed samples. Overexpression of NQO1 was associated with a significantly inferior prognosis. In addition, multivariate analysis suggested that NQO1 overexpression, along with tumor stage and patient age, are prominent prognostic biomarkers for gastric cancer. Moreover, NQO1 overexpression was correlated to a better response to 5-fluorouracil (5-FU)-based adjuvant chemotherapy. CONCLUSION: NQO1 overexpression is associated with a significantly poor prognosis and better response to 5-FU in patients with gastric cancer. These findings are relevant for improving therapeutic approaches for gastric cancer patients.

The diagnostic value of capsule endoscopy in children with intestinal lymphangiectasia.

BACKGROUND: intestinal lymphangiectasia is an unusual cause of protein-losing enteropathy due to either congenital malformation or obstruction of the intestinal lymphatics. However, few reports have investigated the use of video capsule endoscopy in children with intestinal lymphangiectasia. This study was performed to evaluate the diagnostic value of video capsule endoscopy for pediatric intestinal lymphangiectasia. METHODS: in this retrospective study, all patients who underwent video capsule endoscopy between January 2014 and July 2020 were included. Clinical information and video capsule endoscopy data were analyzed. RESULTS: twelve children were enrolled, 7 males and 5 females, with an age at disease onset of 4.5 (range: 3.2-9.3) years and a disease duration of 12.0 (range: 1.3-30.0) months. The most common symptoms were hypoproteinemia (10, 83.3 %), diarrhea (7, 58.3 %), edema (6, 50.0 %), and abdominal pain (3, 25.0 %). Eight patients had low lymphocyte counts, whereas 10 had reduced serum albumin levels (23.2 ± 5.8 g/L). Video capsule endoscopy revealed an overall white snowy appearance due to the presence of whitish, swollen villi in all patients. Regarding the macroscopic lesions of lymphangiectasia, 7 cases involved the entire small bowel from the duodenum to the ileocecal valve, while 5 cases involved part of the small bowel. All patients were treated with medium-chain triglyceride diets, and albumin infusions were administered to 10 patients; sirolimus treatment was administered to 3 patients. At the last follow-up, 5 patients still had hypoalbuminemia and one patient had died of intestinal lymphoma. CONCLUSION: video capsule endoscopy is useful for the diagnosis of intestinal lymphangiectasia and should be applied as a valuable and less invasive examination to confirm or establish a diagnosis.

Pyroptosis-Related lncRNAs Predict the Prognosis and Immune Response in Patients With Breast Cancer.

Background: Breast cancer (BC) is the most common malignant tumor and the leading cause of cancer-related death in women worldwide. Pyroptosis and long noncoding RNAs (lncRNAs) have been demonstrated to play vital roles in the tumorigenesis and development of BC. However, the clinical significance of pyroptosis-related lncRNAs in BC remains unclear. Methods: Using the mRNA and lncRNA profiles of BC obtained from TCGA dataset, a risk model based on the pyroptosis-related lncRNAs for prognosis was constructed using univariate and multivariate Cox regression model, and least absolute shrinkage and selection operator. Patients were divided into high- and low-risk groups based on the risk model, and the prognosis value and immune response in different risk groups were analyzed. Furthermore, functional enrichment annotation, therapeutic signature, and tumor mutation burden were performed to evaluate the risk model we established. Moreover, the expression level and clinical significance of the selected pyroptosis-related lncRNAs were further validated in BC samples. Results: 3,364 pyroptosis-related lncRNAs were identified using Pearson's correlation analysis. The risk model we constructed comprised 10 pyroptosis-related lncRNAs, which was identified as an independent predictor of overall survival (OS) in BC. The nomogram we constructed based on the clinicopathologic features and risk model yielded favorable performance for prognosis prediction in BC. In terms of immune response and mutation status, patients in the low-risk group had a higher expression of immune checkpoint markers and exhibited higher fractions of activated immune cells, while the high-risk group had a highly percentage of TMB. Further analyses in our cohort BC samples found that RP11-459E5.1 was significantly upregulated, while RP11-1070N10.3 and RP11-817J15.3 were downregulated and significantly associated with worse OS. Conclusion: The risk model based on the pyroptosis-related lncRNAs we established may be a promising tool for predicting the prognosis and personalized therapeutic response in BC patients.