Identification of KRAS mutation-associated gut microbiota in colorectal cancer and construction of predictive machine learning model.

Gut microbiota has demonstrated an increasingly important role in the onset and development of colorectal cancer (CRC). Nonetheless, the association between gut microbiota and KRAS mutation in CRC remains enigmatic. We conducted 16S rRNA sequencing on stool samples from 94 CRC patients and employed the linear discriminant analysis effect size algorithm to identify distinct gut microbiota between KRAS mutant and KRAS wild-type CRC patients. Transcriptome sequencing data from nine CRC patients were transformed into a matrix of immune infiltrating cells, which was then utilized to explore KRAS mutation-associated biological functions, including Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways. Subsequently, we analyzed the correlations among these KRAS mutation-associated gut microbiota, host immunity, and KRAS mutation-associated biological functions. At last, we developed a predictive random forest (RF) machine learning model to predict the KRAS mutation status in CRC patients, based on the gut microbiota associated with KRAS mutation. We identified a total of 26 differential gut microbiota between both groups. Intriguingly, a significant positive correlation was observed between Bifidobacterium spp. and mast cells, as well as between Bifidobacterium longum and chemokine receptor CX3CR1. Additionally, we also observed a notable negative correlation between Bifidobacterium and GOMF:proteasome binding. The RF model constructed using the KRAS mutation-associated gut microbiota demonstrated qualified efficacy in predicting the KRAS phenotype in CRC. Our study ascertained the presence of 26 KRAS mutation-associated gut microbiota in CRC and speculated that Bifidobacterium may exert an essential role in preventing CRC progression, which appeared to correlate with the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:proteasome binding. Furthermore, the RF model constructed on the basis of KRAS mutation-associated gut microbiota exhibited substantial potential in predicting KRAS mutation status in CRC patients.IMPORTANCEGut microbiota has emerged as an essential player in the onset and development of colorectal cancer (CRC). However, the relationship between gut microbiota and KRAS mutation in CRC remains elusive. Our study not only identified a total of 26 gut microbiota associated with KRAS mutation in CRC but also unveiled their significant correlations with tumor-infiltrating immune cells, immune-related genes, and biological pathways (Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways). We speculated that Bifidobacterium may play a crucial role in impeding CRC progression, potentially linked to the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:Proteasome binding. Furthermore, based on the KRAS mutation-associated gut microbiota, the RF model exhibited promising potential in the prediction of KRAS mutation status for CRC patients. Overall, the findings of our study offered fresh insights into microbiological research and clinical prediction of KRAS mutation status for CRC patients.

A transcribed ultraconserved noncoding RNA, uc.285+, promotes colorectal cancer proliferation through dual targeting of CDC42 by directly binding mRNA and protein.

The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.

Analysis of differences in intestinal flora associated with different BMI status in colorectal cancer patients.

BACKGROUND: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. METHOD: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. RESULT: There was no significant difference in α diversity and ß diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. CONCLUSIONS: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.

Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target.

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

A comprehensive segmentation of chest X-ray improves deep learning-based WHO radiologically confirmed pneumonia diagnosis in children.

OBJECTIVES: To investigate a comprehensive segmentation of chest X-ray (CXR) in promoting deep learning-based World Health Organization's (WHO) radiologically confirmed pneumonia diagnosis in children. METHODS: A total of 4400 participants between January 2016 and June 2021were identified for a cross-sectional study and divided into primary endpoint pneumonia (PEP), other infiltrates, and normal groups according to WHO's diagnostic criteria. The CXR was divided into six segments of left lung, right lung, mediastinum, diaphragm, ext-left lung, and ext-right lung by adopting the RA-UNet. To demonstrate the benefits of lung field segmentation in pneumonia diagnosis, the segmented images and images that were not segmented, which constituted seven segmentation combinations, were fed into the CBAM-ResNet under a three-category classification comparison. The interpretability of the CBAM-ResNet for pneumonia diagnosis was also performed by adopting a Grad-CAM module. RESULTS: The RA-UNet achieved a high spatial overlap between manual and automatic segmentation (averaged DSC = 0.9639). The CBAM-ResNet when fed with the six segments achieved superior three-category diagnosis performance (accuracy = 0.8243) over other segmentation combinations and deep learning models under comparison, which was increased by around 6% in accuracy, precision, specificity, sensitivity, F1-score, and around 3% in AUC. The Grad-CAM could capture the pneumonia lesions more accurately, generating a more interpretable visualization and enhancing the superiority and reliability of our study in assisting pediatric pneumonia diagnosis. CONCLUSIONS: The comprehensive segmentation of CXR could improve deep learning-based pneumonia diagnosis in childhood with a more reasonable WHO's radiological standardized pneumonia classification instead of conventional dichotomous bacterial pneumonia and viral pneumonia. CLINICAL RELEVANCE STATEMENT: The comprehensive segmentation of chest X-ray improves deep learning-based WHO confirmed pneumonia diagnosis in children, laying a strong foundation for the potential inclusion of computer-aided pediatric CXR readings in precise classification of pneumonia and PCV vaccine trials efficacy in children. KEY POINTS: • The chest X-ray was comprehensively segmented into six anatomical structures of left lung, right lung, mediastinum, diaphragm, ext-left lung, and ext-right lung. • The comprehensive segmentation improved the three-category classification of primary endpoint pneumonia, other infiltrates, and normal with an increase by around 6% in accuracy, precision, specificity, sensitivity, F1-score, and around 3% in AUC. • The comprehensive segmentation gave rise to a more accurate and interpretable visualization results in capturing the pneumonia lesions.

Application of intelligent pacifying strategy information system in reducing short-duration MRI sedation rate in children.

Exploring and analyzing the effectiveness of an intelligent pacifying strategy information system based on assisted decision-making in reducing the sedation rate of children in short-duration magnetic resonance scans. A total of 125 children aged 3-5 years who underwent MRI scans at a children's hospital from July to December 2021 participated in this study, during which 62 children were assigned to a control group from July to September, and 63 children were assigned to an intervention group from October to December. In the intervention group, the pacifier used the intelligent pacifying strategy information system based on assisted decision-making to assess children's temperament, and utilization of a system-generated pacification plan according to assessment results. In the control group, the pacification plan was formulated by the pacifier based on their own experience and discussion with families of the participating children. The success rate of pacification, duration of pacification, and image quality of the two groups were compare. Compared with the control group, the intervention group had a higher success rate of pacification and lower duration of pacification, with statistically significant differences (P < 0.05). There was no difference in image quality between the two groups (P > 0.05). The intelligent pacifying strategy information system can help reduce the use of the sedative drugs in children aged 3-5 years who underwent a short-duration MRI scan.

Mesorectal reconstruction with pedicled greater omental transplantation to relieve low anterior resection syndrome following total intersphincteric resection in patients with ultra-low rectal cancer.

BACKGROUND: Total intersphincteric resection (ISR) is the ultimate anus-preserving surgery for patients with ultra-low rectal cancer (ULRC), which can result in various degrees of anorectal dysfunction. Known as low anterior resection syndrome (LARS), it seriously affects the postoperative quality of life of patients. The aim of this study was to discuss the value of mesorectal reconstruction with pedicled greater omental transplantation (PGOT) to relieve LARS following total ISR in patients with ULRC, hoping to provide new ideas and strategies for the prevention and improvement of LARS. METHODS: We retrospectively analyzed hospitalization data and postoperative anorectal function of 26 ULRC patients, who were met inclusion and exclusion criteria in our center from January 2015 to February 2022. And combined with the results of anorectal manometry and rectal magnetic resonance imaging (MRI) defecography of some patients, we assessed comprehensively anorectal physiological and morphological changes of the patients after surgery, and their correlation with LARS. RESULTS: In this study, 26 patients with ULRC were enrolled and divided into observation group (n = 15) and control group (n = 11) according to whether PGOT was performed. There were no significant differences in surgical results such as operative time, intraoperative blood loss and postoperative complications between the two groups (P > 0.05). Postoperative follow-up showed that patients in both groups showed severe LARS within 3 months after surgery, but from the 3rd month after surgery, LARS in both groups gradually began to decrease, especially in the observation group, which showed faster recovery and better recovery, with statistically significant difference (P < 0.001). Through anorectal manometry, the mean rectal resting pressure in the observation group was significantly lower than that in the control group (P = 0.010). In addition, the postoperative thickness of the posterior rectal mesenterium in the observation group was significantly higher than that in the control group (P = 0.001), and also higher than the preoperative level (P = 0.018). Moreover, rectal MRI defecography showed that the neo-rectum had good compliance under the matting of greater omentum, and its intestinal peristalsis was coordinated. CONCLUSIONS: ULRC patients, with the help of greater omentum, coordinated their neo-rectum peristalsis after total ISR and recovery of LARS was faster and better. PGOT is expected to be an effective strategy for LARS prevention and treatment of ULRC patients after surgery and is worthy of clinical promotion.

Optimal examined lymph node number for accurate staging and long-term survival in rectal cancer: a population-based study.

BACKGROUND: Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC. METHODS: Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I-III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS). RESULTS: The distribution of ELN count between the Chinese registry ( n =7694) and SEER database ( n =21 332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P <0.001; Chinese registry, OR, 1.016, P =0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P <0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival. CONCLUSIONS: A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis.

Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction.

OBJECTIVE: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. METHOD: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. RESULT: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O - glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. CONCLUSIONS: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.

Weighted gene co-expression network analysis identifies the prognosis-related models of left- and right-sided colon cancer.

Left-sided colon cancer (LC) and right-sided colon cancer (RC) are 2 essentially different diseases, and the potential mechanisms regulating them remain unidentified. In this study, we applied weighted gene co-expression network analysis (WGCNA) to confirm a yellow module, mainly enriched in metabolism-related signaling pathways related to LC and RC. Based on the RNA-seq data of colon cancer in The Cancer Genome Atlas (TCGA) and GSE41258 dataset with their corresponding clinical information, a training set (TCGA: LC: n = 171; RC: n = 260) and a validation set (GSE41258: LC: n = 94; RC: n = 77) were divided. Least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis identified 20 prognosis-related genes (PRGs) and helped constructed 2 risk (LC-R and RC-R) models in LC and RC, respectively. The model-based risk scores accurately performed in risk stratification for colon cancer patients. The high-risk group of the LC-R model showed associations with ECM-receptor interaction, focal adhesion, and PI3K-AKT signaling pathway. Interestingly, the low-risk group of the LC-R model showed associations with immune-related signaling pathways like antigen processing and presentation. On the other hand, the high-risk group of the RC-R model showed enrichment for cell adhesion molecules and axon guidance signaling pathways. Furthermore, we identified 20 differentially expressed PRGs between LC and RC. Our findings provide new insights into the difference between LC and RC, and uncover the potential biomarkers for the treatment of LC and RC.

Increased Kremen2 predicts worse prognosis in colon cancer.

Background: Colon cancer (CC) is the fifth most prevalent cancer around the globe and poses a major risk to human health. Even though Kremen2 serves as a prognostic indicator in individuals with malignant tumours, its role in evaluating the prognosis of individuals with colon cancer has not been confirmed. Methods: Here, we examined the protein expression of Kremen2 in CC tissues and paired adjacent normal tissues by immunohistochemistry (IHC), then analyzed the clinical and RNA-seq data presented in The Cancer Genome Atlas (TCGA) database to confirm the relationship between Kremen2 levels and CC. In addition, the associations between Kremen2 mRNA expression and infiltrating immune cells were examined. Results: The study showed that the mRNA expression and protein level of Kremen2 were increased in CC tissues compared with adjacent normal tissues. According to Kaplan-Meier analysis, high Kremen2 expression in CC was linked to poor overall survival and progression-free survival. Clinical correlation analysis highlighted that a high level of Kremen2 expression was strongly linked with tumour progression, particularly lymph node metastasis. Cox regression analysis highlighted that Kremen2 was an independent prognostic indicator for CC. Bioinformatic studies highlighted that Kremen2 might be associated with the immune status in CC. Conclusion: Increased Kremen2 could serve as a potential prognostic CC biomarker.

Update on MRI in pediatric intracranial germ cell tumors-The clinical and radiological features.

Intracranial germ cell tumors (iGCTs) are uncommon brain tumors that mainly occur in children. Differing in histology, location, and gender of the patients, iGCTs are often divided into germinomas and non-germinomatous germ cell tumors (NGGCTs). Early diagnosis and timely treatment are crucial to iGCTs, the subtypes of which have substantial variations. This review summarized the clinical and radiological features of iGCTs at different sites, and reviewed the recent advances in neuroimaging of iGCTs, which can help predict tumor subtypes early and guide clinical decision-making.

Identification of intestinal microbiome associated with lymph-vascular invasion in colorectal cancer patients and predictive label construction.

Objective: To identify differences between the composition, abundance, and biological function of the intestinal microbiome of patients with and without lymph-vascular invasion (LVI) colorectal cancer (CRC) and to construct predictive labels to support accurate assessment of LVI in CRC. Method: 134 CRC patients were included, which were divided into two groups according to the presence or absence of LVI, and their intestinal microbiomes were sequenced by 16SrRNA and analyzed for differences. The transcriptome sequencing data of 9 CRC patients were transformed into immune cells abundance matrix by CIBERSORT algorithm, and the correlation among LVI-associated differential intestinal microbiomes, immune cells, immune-related genes and LVI-associated differential GO items and KEGG pathways were analyzed. A random forest (RF) and eXtreme Gradient Boosting (XGB) model were constructed to predict the LVI of CRC patients based on the differential microbiome. Result: There was no significant difference in α-diversity and ß-diversity of intestinal microbiome between CRC patients with and without LVI (P > 0.05). Linear discriminant analysis Effect Size (LEfSe) analysis showed 34 intestinal microbiomes enriched in CRC patients of the LVI group and 5 intestinal microbiomes were significantly enriched in CRC patients of the non-lymph-vascular invasion (NLVI) group. The RF and XGB prediction models constructed with the top 15% of the LVI-associated differential intestinal microbiomes ranked by feature significance had good efficacy. Conclusions: There are 39 intestinal flora with significantly different species abundance between the LVI and NLVI groups. g:Alistipes.s:Alistipes_indistinctus is closely associated with colorectal cancer vascular invasion. LVI-associated differential intestinal flora may be involved in regulating the infiltration of immune cells in CRC and influencing the expression of immune-related genes. LVI-associated differential intestinal flora may influence the process of vascular invasion in CRC through a number of potential biological functions. RF prediction models and XGB prediction models constructed based on microbial markers of gut flora can be used to predict CRC-LVI conditions.

Automated measurement of leg length discrepancy from infancy to adolescence based on cascaded LLDNet and comprehensive assessment.

Background: Deep learning (DL) has been suggested for the automated measurement of leg length discrepancy (LLD) on radiographs, which could free up time for pediatric radiologists to focus on value-adding duties. The purpose of our study was to develop a unified solution using DL for both automated LLD measurements and comprehensive assessments in a large and comprehensive radiographic dataset covering children at all stages, from infancy to adolescence, and with a wide range of diagnoses. Methods: The bilateral femurs and tibias were segmented by a cascaded convolutional neural network (CNN), referred to as LLDNet. Each LLDNet was conducted through use of residual blocks to learn more abundant features, a residual convolutional block attention module (Res-CBAM) to integrate both spatial and channel attention mechanisms, and an attention gate structure to alleviate the semantic gap. The leg length was calculated by localizing anatomical landmarks and computing the distances between them. A comprehensive assessment based on 9 indices (5 similarity indices and 4 stability indices) and the paired Wilcoxon signed-rank test was undertaken to demonstrate the superiority of the cascaded LLDNet for segmenting pediatric legs through comparison with alternative DL models, including ResUNet, TransUNet, and the single LLDNet. Furthermore, the consistency between the ground truth and the DL-calculated measurements of leg length was also comprehensively evaluated, based on 5 indices and a Bland-Altman analysis. The sensitivity and specificity of LLD >5 mm were also calculated. Results: A total of 976 children were identified (0-19 years old; male/female 522/454; 520 children between 0 and 2 years, 456 children older than 2 years, 4 children excluded). Experiments demonstrated that the proposed cascaded LLDNet achieved the best pediatric leg segmentation in both similarity indices (0.5-1% increase; P<0.05) and stability indices (13-47% percentage decrease; P<0.05) compared with the alternative DL methods. A high consistency of LLD measurements between DL and the ground truth was also observed using Bland-Altman analysis [Pearson correlation coefficient (PCC) =0.94; mean bias =0.003 cm]. The sensitivity and specificity established for LLD >5 mm were 0.792 and 0.962, respectively, while those for LLD >10 mm were 0.938 and 0.992, respectively. Conclusions: The cascaded LLDNet was able to achieve promising pediatric leg segmentation and LLD measurement on radiography. A comprehensive assessment in terms of similarity, stability, and measurement consistency is essential in computer-aided LLD measurement of pediatric patients.

Case Report: Colon malignant tumor caused by retroperitoneal small round cell undifferentiated sarcoma.

Small round cell undifferentiated sarcoma is a rare and highly invasive group of malignant bone and soft tissue tumors, often associated with a high misdiagnosis rate. The patient in this case was a 34-year-old male who presented with a two-month history of abdominal pain that worsened over the past two weeks. Elevated levels of tumor markers CA19-9 and CA72-4 were observed. Imaging revealed a substantial, well-vascularized mass in the lower left abdomen, located in the posterior abdominal cavity, invading the descending colon and the root of the small mesentery, and infiltrating the serous layer. The lesion was extensively resected without any postoperative complications. Microscopic examination indicated a combination of mucinous adenocarcinoma (approximately 30%) and small round cell undifferentiated sarcoma (approximately 70%). The patient was followed up for six months, and one month after surgery, a recurrence of the tumor was observed in the left paracolonic sulcus area, with metastases to the abdominal wall, peritoneum, and medial iliac muscles. Chemotherapy and targeted therapy were administered, and the patient currently survives with the presence of tumors. Small round cell undifferentiated sarcoma is an uncommon and highly invasive tumor, and clinical surgeons need to raise their awareness and realize to the maximum extent possible that this disease can be described through a multi-modal combination of immunohistochemistry and genetic test to improve diagnostic accuracy and reduce missed diagnoses. Further research in the field of biology is necessary to explore targeted drugs specifically suitable for this disease.

Comprehensive multi-omics analysis of the m7G in pan-cancer from the perspective of predictive, preventive, and personalized medicine.

Background: The N7-methylguanosine modification (m7G) of the 5' cap structure in the mRNA plays a crucial role in gene expression. However, the relation between m7G and tumor immune remains unclear. Hence, we intended to perform a pan-cancer analysis of m7G which can help explore the underlying mechanism and contribute to predictive, preventive, and personalized medicine (PPPM / 3PM). Methods: The gene expression, genetic variation, clinical information, methylation, and digital pathological section from 33 cancer types were downloaded from the TCGA database. Immunohistochemistry (IHC) was used to validate the expression of the m7G regulator genes (m7RGs) hub-gene. The m7G score was calculated by single-sample gene-set enrichment analysis. The association of m7RGs with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. CellProfiler was used to extract pathological section characteristics. XGBoost and random forest were used to construct the m7G score prediction model. Single-cell transcriptome sequencing (scRNA-seq) was used to assess the activation state of the m7G in the tumor microenvironment. Results: The m7RGs were highly expressed in tumors and most of the m7RGs are risk factors for prognosis. Moreover, the cellular pathway enrichment analysis suggested that m7G score was closely associated with invasion, cell cycle, DNA damage, and repair. In several cancers, m7G score was significantly negatively correlated with MSI and TMB and positively correlated with TIDE, suggesting an ICB marker potential. XGBoost-based pathomics model accurately predicts m7G scores with an area under the ROC curve (AUC) of 0.97. Analysis of scRNA-seq suggests that m7G differs significantly among cells of the tumor microenvironment. IHC confirmed high expression of EIF4E in breast cancer. The m7G prognostic model can accurately assess the prognosis of tumor patients with an AUC of 0.81, which was publicly hosted at https://pan-cancer-m7g.shinyapps.io/Panca-m7g/. Conclusion: The current study explored for the first time the m7G in pan-cancer and identified m7G as an innovative marker in predicting clinical outcomes and immunotherapeutic efficacy, with the potential for deeper integration with PPPM. Combining m7G within the framework of PPPM will provide a unique opportunity for clinical intelligence and new approaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00305-1.

The correction factor of Monterey No. 0/30 sample with fines content liquefaction resistance between cyclic triaxial and cyclic hollow cylinder tests.

Soil liquefaction is one of the most detrimental forms of earthquake-induced ground failure that can result in catastrophic damage to engineering structures. For the seismic safety evaluation of foundations and high-rise structures, it is the most critical way to assess liquefaction resistance. In this paper, an array number of isotropically consolidated undrained cyclic triaxial tests (CTT) and cyclic hollow cylinder tests (CHCT) have been performed to evaluate soil liquefaction resistance. Thirty-seven isotopically consolidated undrained cyclic triaxial tests and thirty-seven cyclic hollow cylinder tests were run on the uniform medium Monterey No. 0/30 sand and it is with four different percentages of fine content. By using cyclic triaxial and cyclic hollow cylinder tests for evaluating liquefaction resistance, it helps us better understand the relationship between two types of tests on uniform clean Monterey No. 0/30 sand and soil sample with five different percentages of fines content. Four different relative densities of 30%, 45%, 50%, and 60%, two confining pressure of 103 kpa and 207 kpa, and five cyclic stress ratios (0.15, 0.2, 0.25, 0.3, and 0.4) have been used for a series of cyclic triaxial tests and cyclic hollow cylinder tests. At the same relative densities of 30% and 60%, the correction factor between CTT and CHCT evaluated ranged from 0.46 to 0.63 on the uniform clean Monterey No. 0/30 sand. Statistical analyses were performed to formulate functional relationships for predicting the correction factor of soil liquefaction resistance between CTT and CHCT tests.

Preoperative Neutrophil-BMI Ratio As a Promising New Marker for Predicting Tumor Outcomes in Colorectal Cancer.

Background: Inflammation and nutritional status are highly associated with colorectal cancer (CRC) prognosis. This study aimed to evaluate the prognostic value of the preoperative neutrophil-BMI ratio (NBR) in patients with CRC. Methods: A retrospective analysis was performed on 2471 patients with CRC who underwent surgical resection between 2004 and 2019. Patients were divided into two groups based on the cutoff value for NBR. Cox regression and Kaplan-Meier curves were used to evaluate overall survival (OS). Results: High NBR was associated with female sex, low BMI, colon, right-sided CRC, poor differentiation, T3 to 4 stage, M1 to 2 stage, high carcinoembryonic antigen (CEA) level, III-IV stage, microsatellite instability (MSI), and no adjuvant chemotherapy (all P < .05). The high NBR group had a shorter OS than the low NBR group. Female and right sided patients with CRC and with high NBR had a worse prognosis. Univariate Cox regression suggested that NBR was significantly associated with poor prognosis. Multivariate analysis confirmed that age (P = .019,HR:1.012), differentiation (P = .001,HR:1.306), TNM stage (P < .001,HR:2.432), CEA (P = .014,HR:1.001), and NBR (P < .001, HR: 3.309) were independent poor prognostic factors for OS. Subgroup univariate analysis indicated that female patients with high NBR had a worse prognosis. A nomogram composed of TNM stage, CEA, and NBR was developed, and internal validation was based on female patients with CRC. The nomogram provided good discrimination for both the training and validation sets, with area under the curve values of 0.79 and 0.769, respectively. Conclusions: High preoperative levels of NBR are indicators of poor prognosis in patients with CRC.

Advantages of total proctocolectomy with straight ileoanal anastomosis plus pedicled omental transposition for familial adenomatous polyposis: a preliminary study.

PURPOSE: To achieve excellent postoperative bowel function in familial adenomatous polyposis (FAP) patients, it is important to reconstruct the digestive tract. The aim of this study is to preliminarily discuss the advantages of total proctocolectomy with straight ileoanal anastomosis (TPC-SIAA) plus pedicled omental transposition for FAP. METHODS: A retrospective study was carried out in two hospitals analysing data for FAP patients who underwent surgical treatments between 2015 and 2021. Perioperative outcomes and early and mid-term anal functions were analysed. RESULTS: After excluding 4 patients who underwent total proctocolectomy with permanent ileostomy, 10 patients were enrolled in the study. Among the 10 patients, 3 received TPC-SIAA plus pedicled omental transposition, 3 received total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA), and 4 received total colectomy with ileal pouch-rectal anastomosis (TC-IPRA). Except for one case conversion to laparotomy, laparoscopic surgery was performed for the other cases. The incidence of early postoperative complications was apparently higher with pouch anastomosis (57.1%) than straight anastomosis (0%). Frequencies of bowel movement and low anterior resection syndrome (LARS) score were higher for TPC-SIAA than the other two surgical procedures in the early term; over time, however, the frequencies of bowel movement and LARS score both showed a decreasing trend. In addition, combined with anorectal pressure detection and magnetic resonance imaging defecography at the 3rd month after TPC-SIAA plus pedicled omental transposition, defecation coordination was good. The dynamics and receptivity of the new rectum tended to be as expected. CONCLUSION: Although the three surgical procedures are safe and feasible surgical options for FAP, TPC-SIAA plus pedicled omental transposition is more consistent with intestinal physiology, with good intestinal compliance, and anal function tended to be as expected over time. Nevertheless, more extensive studies are needed to confirm these benefits.