The study on circRNA profiling uncovers the regulatory function of the hsa_circ_0059665/miR-602 pathway in breast cancer.

Abnormal expression of circRNAs has been observed in different types of carcinomas, and they play significant roles in the biology of these cancers. Nevertheless, the clinical relevance and functional mechanisms of the majority of circRNAs implicated in breast cancer progression remain unclear. The primary objective of our investigation is to uncover new circRNAs in breast cancer and elucidate the underlying mechanisms by which they exert their effects. The circRNA expression profile data for breast cancer and RNA-sequencing data were acquired from distinct public databases. Differentially expressed circRNAs and mRNA were identified through fold change filtering. The establishment of the competing endogenous RNAs (ceRNAs) network relied on the interplay between circular RNAs, miRNAs, and mRNAs. The hub genes were identified from the protein-protein interaction (PPI) regulatory network using the CytoHubba plugin in Cytoscape. Moreover, the expression levels and prognostic value of these hub genes in the PPI network were assessed using the GEPIA and Kaplan-Meier plotter databases. Fluorescence in situ hybridization (FISH) was used to identified the expression and intracellular localization of hsa_circ_0059665 by using the tissue microarray. Transwell analysis and CCK-8 analysis were performed to assess the invasion, migration, and proliferation abilities of breast cancer cells. Additionally, we investigated the interactions between hsa_circ_0059665 and miR-602 through various methods, including FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Rescue experiments were conducted to determine the potential regulatory role of hsa_circ_0059665 in breast cancer progression. A total of 252 differentially expressed circRNAs were identified. Among them, 246 circRNAs were up-regulated, while 6 circRNAs were down-regulated. Based on prediction and screening of circRNA-miRNA and miRNA-mRNA binding sites, we constructed a network consisting of circRNA-miRNA-mRNA interactions. In addition, we constructed a Protein-Protein Interaction (PPI) network and identified six hub genes. Moreover, the expression levels of these six hub genes in breast cancer tissues were found to be significantly lower. Furthermore, the survival analysis results revealed a significant correlation between low expression levels of KIT, FGF2, NTRK2, CAV1, LEP and poorer prognosis in breast cancer patients. The FISH experiment results indicated that hsa_circ_0059665 exhibits significant downregulation in breast cancer, and its decreased expression is linked to poor prognosis in breast cancer patients. Functional in vitro experiments revealed that overexpression of hsa_circ_0059665 can inhibit proliferation, migration and invasion abilities of breast cancer cells. Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells.

Mortality risk of patients with intestinal obstruction.

BACKGROUND: Intestinal obstruction represents a severe intestinal disease associated with higher mortality rates. However, the determinants of mortality in patients with intestinal obstruction remain inadequately understood. This study sought to elucidate the potential risk factors associated with mortality in the context of intestinal obstruction during the COVID-19 pandemic. METHODS: A retrospective analysis was performed on a cohort of 227 patients diagnosed with intestinal obstruction at the First Hospital of Hebei Medical University, spanning the period from September 7, 2022, to January 7, 2023. The primary endpoint of the study was mortality within four weeks following discharge. Univariate and multivariable logistic regression models were utilized to evaluate the risk factors associated with mortality outcomes. RESULTS: A cohort of 227 patients diagnosed with intestinal obstruction (median age, 59.02 years [IQR, 48.95-70.85 years]) was included in our study. Malignant bowel obstruction (MBO) and COVID-19 were identified as independent risk factors for mortality among these patients. Notably, the mortality rate increased significantly to 38.46% when MBO was concomitant with COVID-19. Furthermore, postoperative pulmonary complications (PPC) (OR, 54.21 [death]; 95% CI, 3.17-926.31), gastric cancer (OR, 9.71 [death]; 95% CI, 1.38-68.18), VTE (Caprini Score ≥ 5) (OR, 7.64 [death]; 95% CI, 1.37-42.51), and COVID-19 (OR, 5.72 [death]; 95% CI, 1.01-32.29) were all determined to be independent risk factors for postoperative mortality. Additionally, gastric cancer could have emerged as one of the most severe risk factors for mortality in individuals with intestinal obstruction within the cohort of cancer patients, of which gastric cancer exhibited higher mortality rates compared to individuals with other forms of cancer. CONCLUSION: The study identifies MBO, gastric cancer, COVID-19, PPC, and VTE as potential risk factors for mortality in cases of intestinal obstruction. These findings highlight the necessity for continuous monitoring of indicators related to these mortality risk factors and their associated complications, thereby offering valuable insights for the management and treatment of intestinal obstruction.

Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers.

Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.

Unilateral severe gynecomastia in a 14 year-old adolescent with neurofibromatosis type 1 undergoing endoscopic mastectomy: a case report.

Gynecomastia can be caused by neurofibromas but has rarely been reported. The present case report describes the clinical appearance, diagnosis, and therapy of a rare combination of a 14 year-old adolescent male unilateral severe gynecomastia with NF-1 neurofibromatosis. In this particular case, we successfully performed minimally invasive surgery using endoscopic mastectomy, which not only resulted in a satisfactory appearance but also confirmed the presence of neurofibroma type 1 by detecting typical immunohistochemical indicators associated with the disease. Additionally, we analyzed the gene responsible for the disease, c.1431del: p. F477Lfs*21, based on the patient's family history.

Bifidobacterium longum suppresses colorectal cancer through the modulation of intestinal microbes and immune function.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target.

Copy number alterations are crucial for the development of gastric cancer (GC). Here, we identified Transmembrane Protein 65 (TMEM65) amplification by genomic hybridization microarray to profile copy-number variations in GC. TMEM65 mRNA level was significantly up-regulated in GC compared to adjacent normal tissues, and was positively associated with TMEM65 amplification. High TMEM65 expression or DNA copy number predicts poor prognosis (P < 0.05) in GC. Furtherly, GC patients with TMEM65 amplification (n = 129) or overexpression (n = 78) significantly associated with shortened survival. Ectopic expression of TMEM65 significantly promoted cell proliferation, cell cycle progression and cell migration/invasion ability, but inhibited apoptosis (all P < 0.05). Conversely, silencing of TMEM65 in GC cells showed opposite abilities on cell function in vitro and suppressed tumor growth and lung metastasis in vivo (all P < 0.01). Moreover, TMEM65 depletion by VNP-encapsulated TMEM65-siRNA significantly suppressed tumor growth in subcutaneous xenograft model. Mechanistically, TMEM65 exerted oncogenic effects through activating PI3K-Akt-mTOR signaling pathway, as evidenced of increased expression of key regulators (p-Akt, p-GSK-3ß, p-mTOR) by Western blot. YWHAZ (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase) was identified as a direct downstream effector of TMEM65. Direct binding of TMEM65 with YWHAZ in the cytoplasm inhibited ubiquitin-mediated degradation of YWHAZ. Moreover, oncogenic effect of TMEM65 was partly dependent on YWHAZ. In conclusion, TMEM65 promotes gastric tumorigenesis by activating PI3K-Akt-mTOR signaling via cooperating with YWHAZ. TMEM65 overexpression may serve as an independent new biomarker and is a therapeutic target in GC.

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study.

While Salvia chinensis Benth (commonly known as "Shijianchuan" in Chinese, and abbreviated as SJC) is commonly used in adjuvant therapy for colorectal cancer (CRC) in traditional Chinese medicine, its mechanism of action remains unclear. In this study, Initially, we examined the impact of SJC on CRC cells in an in vitro setting. Next, we initially retrieved the primary active components and targets of SJC from databases such as TCMSP and existing literature. Subsequently, we integrated differential gene expression data from the GEO database and collected CRC-related targets from resources like DisGeNET. The matching of these datasets enabled the identification of SJC-CRC targets. We constructed a protein-protein interaction network and identified core targets through topological analysis. GO and KEGG enrichment analyses were performed using clusterProfiler. We established networks linking traditional Chinese medicine components to targets and core targets to signaling pathways. Additionally, we performed molecular docking to validate interactions between the main compounds and targets, and employed Western blot analysis to explore how the major components of SJC affect crucial signaling pathways. In this study, SJC inhibited the viability of HCT-116 and HT-29 cells. We identified a total of 11 active components in SJC along with 317 target genes. Among these, there were 8612 target genes associated with CRC, and we successfully matched 276 SJC-CRC target genes. Through topological analysis of the protein-protein interaction network, we pinpointed 20 core targets. It was revealed that SJC effects are linked to genes governing processes like cell apoptosis, proliferation, hypoxia, oxidative stress, and signaling pathways such as PI3K-Akt through GO and KEGG pathway enrichment analyses. Additionally, we applied molecular docking techniques and observed that the majority of active compounds displayed robust binding affinity with the selected targets. In vitro experiments suggested that SJC and its key component, Ursolic acid, may exert its anti-CRC effects by modulating the core PI3K/AKT signaling pathway through inhibiting the phosphorylation of the target Akt1. This discovery is consistent with the predictions derived from network pharmacology methods. This study marks the inaugural utilization of bioinformatics methods in conjunction with in vitro experiments to comprehensively investigate the pharmacological and molecular mechanisms responsible for SJC anti-CRC effects.

Identification of Hypoxia-Associated Signature in Colon Cancer to Assess Tumor Immune Microenvironment and Predict Prognosis Based on 14 Hypoxia-Associated Genes.

Purpose: Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer. Methods: Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level. Results: A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells. Conclusion: Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.

FABP4 Regulates Cell Proliferation, Stemness, Apoptosis, and Glycolysis in Colorectal Cancer via Modulating ROS/ERK/mTOR Pathway.

BACKGROUND: Colorectal cancer is a common digestive tract malignancy. This study aimed to expound the functional role of fatty-acid-binding protein 4 (FABP4) and the potential underlying mechanisms in the development of colorectal cancer. METHODS: Several techniques were utilized to investigate the role of FABP4 in colorectal cancer. FABP4 mRNA expression was quantified using Real time-quantitative PCR (RT-qPCR). Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), sphere formation assays and flow cytometry evaluated cell growth, stemness, and apoptosis in SW480 and HT29 cells. Glycolysis was assessed via extracellular acidification rate (ECAR) , lactate production, glucose uptake, adenosine triphosphate (ATP)/adenosine 5'-diphosphate (ADP) ratio, and Glut1 and Elevated lactate dehydrogenase A (LDHA) protein expression. Reactive oxygen species (ROS) levels were analyzed by flow cytometry. Western blot measured the protein expression of FABP4, Proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, Glut1, LDHA, stemness makers (Sox2, Oct4, and ALDHA1), and extracellular regulated protein kinase (ERK)/mammalian target of rapamycin (mTOR) pathway proteins. In vivo experiments, BALB/c nude mice (n = 12) were inoculated with 200 µL HT29 cells (5 × 106 cells) transfected with sh-FABP4 or short hairpin (sh)-negative control (NC), forming two groups with 6 mice each. The in vivo mice tumor model allowed for evaluating FABP4's impact on tumor growth. RESULTS: FABP4 was significantly upregulated in colorectal cancer tissues and cells (p < 0.05). FABP4 knockdown markedly inhibited cell proliferation, stemness, and glycolysis, while promoting apoptosis in these cells (p < 0.05). Additionally, FABP4 depletion led to a significant increase in ROS level (p < 0.05). However, N-acetyl-L-cysteine (NAC) (p < 0.05), a ROS scavenger, mitigates these effects. Furthermore, the effects of FABP4 depletion on cell growth, stemness, glycolysis, and apoptosis in colorectal cancer cells were also retarded by NAC (p < 0.05). Notably, FABP4 knockdown also suppressed the ERK/mTOR pathway, suggesting its regulation via ROS (p < 0.05). In vivo study results showed, FABP4 depletion significantly curbed tumor growth in colorectal cancer (p < 0.05). CONCLUSIONS: These results suggest that FABP4 depletion inhibits colorectal cancer progression by modulating cell growth, stemness, glycolysis and apoptosis. This regulation occurs through the ROS/ERK/mTOR pathway.

APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy.

p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. As there is currently no existing study on combining APR-246 with radiation in rectal cancer, our objective was to investigate whether APR-246 could enhance the sensitivity of colorectal cancer cells, regardless of their p53 status, to radiation treatment. The combination treatment had synergistic effects on HCT116p53-R248W/- (p53Mut) cells, followed by HCT116p53+/+ [wild-type p53 (p53WT)] cells, and exhibited an additive effect on HCT116p53-/- (p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared with p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radiosensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in patients with rectal cancer.

The combination of endoscopic subcutaneous mastectomy and liposuction (Liu and Shang's 2-hole 7-step method) as the treatment of gynecomastia.

BACKGROUND: Most patients suffering from gynecomastia require treatment to maintain a smooth subcutaneous tissue contour, remove loose skin, and leave a suitable nipple-areolar complex with minimal scarring; hence, surgery has become the prime choice to treat gynecomastia. Based on our experience, Liu and Shang's 2-hole 7-step method works well for these patients. METHODS: From November 2021 to November 2022, a total of 101 gynecomastia patients featuring various Simon grades were included in this study. The patients' basic condition and surgical procedure were recorded in detail. A score of 1 to 5 was given for 6 main aesthetic aspects. RESULTS: With Liu and Shang's 2-hole 7-step method, the operations were successfully completed in all 101 patients. Six patients had Simon grade I, 21 grade IIA, 56 grade IIB, and 18 grade III. The average surgery time was 86.54 (range = 46-144) minutes. The average intraoperative blood loss was 22.7 (range = 10 ∼ 75) mL. The average postoperative drainage time was 2.35 (range = 1-4) days, the drainage volume was 83.35 (range = 13∼240) mL, and the drainage mainly occurred on the first postoperative day. The scores on all 6 aesthetic aspects were >4 points, which fully affirmed the aesthetic effect of this method. CONCLUSION: Liu and Shang's 2-hole 7-step method is safe and feasible for treating gynecomastia and has been fully affirmed for its efficacy and cosmetic effect. It can be the main option for minimally invasive surgery to treat gynecomastia.

Metabolic Syndrome and Its Components are Associated with In-Hospital Complications after Thoracic Endovascular Aortic Repair for Acute Type B Aortic Dissection.

BACKGROUND: This study aimed to explore whether and to what extent metabolic syndrome (MetS) and its components are associated with in-hospital complications in patients with acute type B aortic dissection after thoracic endovascular aortic repair (TEVAR). METHODS: We retrospectively enrolled 684 patients who had undergone TEVAR. Demographic and clinical data were collected and subgroup analysis, mixed-model regression analysis, scoring systems, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Overall, 684 inpatients were assigned to the poor outcome (n = 90) or no complications (n = 594) group. Compared to the no complications group, the poor outcome group had a higher incidence of MetS (44 [48.9%] vs. 120 [20.2%], P < 0.05). In the subgroup analysis, in-hospital complications were present in 3.1%, 6.6%, 11.9%, 20.7%, 40.0%, and 62.5% of patients in the 6 groups who met the 0, 1, 2, 3, 4, and 5 MetS diagnostic criteria, respectively. On multivariable logistic regression, hypertension (odds ratio [OR]: 2.680; 95% confidence interval [CI]: 1.571-4.570), type 2 diabetes (OR: 2.135; 95% CI: 1.192-3.824), quartiles of body mass index (OR: 1.801; 95% CI: 1.415-2.291), high-density lipoprotein cholesterol (OR: 0.763; 95% CI: 0.611-0.953), and systolic blood pressure (OR: 1.894; 95% CI: 1.486-2.413) were independent factors for in-hospital complications after adjustment for other risk factors. After adjusting for potential confounding factors, MetS was an independent risk factor for in-hospital complications. We established a scoring system for each component and the area under the ROC curve was 0.664 (95% CI: 0.618-0.710) in all patients, 0.672 (95% CI: 0.595-0.749) in patients with MetS, and 0.610 (95% CI: 0.552-0.667) in patients without MetS, as determined by ROC analysis. CONCLUSIONS: MetS, especially the blood pressure component, confers a greater risk of in-hospital complications in patients with acute type B aortic dissection after TEVAR.

Comprehensive analysis of the differences between left- and right-side colorectal cancer and respective prognostic prediction.

BACKGROUND: Previous studies have reported that the tumor heterogeneity and complex oncogenic mechanisms of proximal and distal colon cancer (CRC) are divergent. Therefore, we aim to analyze the differences between left-sided CRC (L_cancer) and right-sided CRC (R_cancer), as well as constructing respective nomograms. METHODS: We enrolled 335 colon cancer patients (146 L_cancer patients and 189 R_cancer patients) from The Cancer Genome Atlas (TCGA) data sets, and 102 pairs of color cancer tissue and adjacent normal tissue (51 L_cancer patients and 51 R_cancer patients) from our hospital. Firstly, we analyzed the differences between the L_cancer patients and R_cancer patients, and then established the L_cancer and R_cancer prognostic models using LASSO Cox. RESULTS: R_cancer patients had lower survival than L_cancer patients. R_cancer patients had higher ESTIMATE and immune scores and lower tumor purity. These patterns of expression of immune checkpoint-related genes and TMB level were higher in R_cancer than in L_cancer patients. Finally, we using Lasso Cox regression analyses established a prognostic model for L_cancer patients and a prognostic model for R_cancer patients. The AUC values of the risk score for OS in L_cancer were 0.862 in the training set and 0.914 in the testing set, while those in R_cancer were 0.835 in the training set and 0.857 in the testing set. The AUC values in fivefold cross-validation were between 0.727 and 0.978, proving that the two prognostic models have great stability. The nomogram of L_cancer included prognostic genes, age, pathological M, pathological stage, and gender, the AUC values of which were 0.800 in the training set and 0.905 in the testing set. Meanwhile, the nomogram of R_cancer comprised prognostic genes, pathological N, pathological T, and age, the AUC values of which were 0.836 in the training set and 0.850 in the testing set. In the R_cancer patients, high-risk patients had a lower proportion of 'B cells memory', 'Dendritic cells resting', immune score, ESTIMATE score, immune checkpoint-related genes, and HLA-family genes, and a higher proportion of 'T cells follicular helper', 'Dendritic cells activated', and 'Mast cells activated'. CONCLUSIONS: We found significant differences between L_cancer and R_cancer patients and established a clinical predictive nomogram for L_cancer patients and a nomogram for R_cancer patients. Additionally, R_cancer patients in low-risk groups may be more beneficial from immunotherapy.

Effects of Let-7c on the processing of hepatitis B virus associated liver diseases.

BACKGROUND: The most common type of cancer of the digestive system is hepatocellular carcinoma. In China, many patients harbour HBV. The lin28B/Let-7c/MYC axis is associated with the occurrence of many cancers. Therefore, we aimed to illuminate the function of the lin28B/Let-7c/MYC axis in hepatocellular carcinoma. We aimed to evaluate the critical involvement of lin28B and Let-7c in the carcinogenesis of human hepatocellular carcinoma (B-HCC). METHODS: Data from the GEO database were used to analyse differentially expressed genes and IRGs. A protein - protein interaction (PPI) network and Venn diagram were generated to analyse relationships. Real-time RT-PCR, Western blotting, and cell counting kit-8 assays were used to examine the association of lin28B, Let-7c, and MYC with cell proliferation. RESULTS: A total of 2552 functionally annotated differentially expressed RNAs were analysed in HBV patients from the GSE135860 database. In addition, 46 let-7c target genes were screened in HBV patients, and the interactions were analysed through PPI network analysis. The results confirmed that Let-7c and its target genes play a key role in HBV-related diseases. Next, we discovered a gradual decrease in Let-7c expression during the progression from HBV-associated chronic hepatitis (B-CH) and HBV-associated liver cirrhosis (B-LC) to B-HCC. We found evidence for a negative association between lin28B expression and Let-7c expression. The expression of MYC was obviously upregulated when Let-7c was inhibited. CONCLUSION: Our results highlight that Let-7c and lin28B participate in the carcinogenesis of HBV-associated diseases through the lin28B/Let-7c/MYC axis.

Metabolic syndrome and its components are associated with hypoxemia after surgery for acute type A aortic dissection: an observational study.

BACKGROUND: The aim of this study was to explore whether or to what extent metabolic syndrome (METs) and its components were associated with hypoxemia in acute type A aortic dissection (ATAAD) patients after surgery. METHODS: This study involved 271 inpatients who underwent surgery. Demographic and clinical data were collected. Subgroup analysis, mixed model regression analysis, and receiver operating characteristic (ROC) curve analysis were performed, and a scoring system was evaluated. RESULTS: The 271 inpatients were assigned to the hypoxemia group (n = 48) or no hypoxemia group (n = 223) regardless of METs status. Compared to the no hypoxemia group, the hypoxemia group had a higher incidence of METs. Hypoxemia was present in 0%, 3.7%, 19.8%, 51.5%, 90.0% and 100% in the groups of individuals who met the diagnostic criteria of MetS 0, 1, 2, 3, 4 and 5 times, respectively. In the multivariable logistic regression analysis, BMI quartile was still a risk factor for hypoxemia after adjustment for other risk factors. After adjustment for potential confounding factors, METs was an independent risk factor for hypoxemia in several models. After assigning a score for each METs component present, the AUCs were 0.852 (95% CI 0.789-0.914) in all patients, 0.728 (95% CI 0.573-0.882) in patients with METs and 0.744 (95% CI 0.636-0.853) in patients without METs according to receiver operating characteristic analysis. CONCLUSIONS: METs, especially body mass index, confers a greater risk of hypoxemia in ATAAD after surgery.

miR-17-5p promotes the invasion and migration of colorectal cancer by regulating HSPB2.

MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. A significant upregulation of miR-17-5p expression was found in colorectal cancer (CRC) tissues by miRNA microarray chip analysis. However, the underlying mechanism of miR-17-5p in CRC is still unclear. The mRNA expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. The biological function of miR-17-5p was demonstrated through CCK-8, colony formation, flow cytometry and transwell assays. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. Transcriptome sequencing and miRNA target prediction software suggested that HSPB2 might be a target gene of miR-17-5p and luciferase reporter detection validated for the first time that miR-17-5p binds directly to the 3'-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2. Taken together, miR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.

Comprehensive analysis of N6-methylandenosine regulators and m6A-related RNAs as prognosis factors in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies and has been a leading cause of cancer-related death worldwide in recent years. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification of various types of RNAs, and it plays a vital role in promoting cancer development. Here, we obtained SNV and transcriptome data of CRC from The Cancer Genome Atlas (TCGA). We demonstrated that most m6A methylation regulators were aberrantly expressed in individuals with CRC. The abnormal expression of m6A regulators was caused by their different copy number variation (CNV) patterns, and alteration of m6A regulators was significantly correlated with prognosis and tumor stage. By using weighted coexpression network analysis (WGCNA), we identified m6A-related long noncoding RNAs (lncRNAs) and mRNAs; then we used least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct m6A-related lncRNA and mRNA prognostic signatures in the TCGA dataset. Furthermore, a nomogram with clinicopathological features, lncRNA risk scores, and mRNA risk scores was established, which showed a strong ability to forecast the overall survival of the individuals with CRC in training and testing sets. In conclusion, m6A methylation regulators played a vital role in affecting the prognosis of subjects with CRC, and m6A-related lncRNAs and mRNAs revealed underlying mechanisms in CRC tumorigenesis and progression.

ITGB4 as a novel serum diagnosis biomarker and potential therapeutic target for colorectal cancer.

PURPOSE: To develop new and effective biomarkers for the diagnosis of colorectal cancer (CRC). EXPERIMENTAL DESIGN: The serum expression of ITGB4 (49 CRC and 367 HC) was detected by enzyme-linked immunosorbent assay (ELISA), and its diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. The sensitivity and specificity of ITGB4 in CRC diagnosis were calculated through statistical analysis. The optimal clinical cutoff value was calculated using the Youden index, and diagnostic efficacy was analyzed in a larger serum sample (98 CRC and 1631 non-CRC). The expression of ITGB4 was measured by CyTOF (cell experimental technology) at the single-cell level, and characteristics were analyzed using viSNE and SPADE TREE. RESULTS: Serum ITGB4 and CEA levels were significantly higher in CRC patients than in HC and non-CRC patients. The use of serum ITGB4 levels for the diagnosis of CRC has a high sensitivity (79%) but not high specificity when the clinical cutoff value was 0.70 ng/mL. However, the optimal cutoff value was 1.6 ng/mL with 86.2% specificity and 52.0% sensitivity, and the diagnostic efficacy was greatly improved with high specificity (82.0%) and sensitivity (71.4%) when combined with CEA. ITGB4 expression characteristics were measured and related to the expression of EpCAM, Ck8/18, and perforin at the single-cell level. Single-cell analysis showed that cell clusters with low expression of CK8/18 and ITGB4 were more sensitive to 5FU and radiotherapy (RT). CONCLUSIONS: ITGB4 is an effective diagnostic serum biomarker and a potential therapeutic target for CRC.

Identification of prognostic immune-related gene signature associated with tumor microenvironment of colorectal cancer.

BACKGROUND: The tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC). METHODS: Transcriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database. RESULTS: Gene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717-0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates. CONCLUSIONS: In this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.

Two New Methods of Supine Venographically Guided Popliteal Vein Puncture: A Retrospective Study.

OBJECTIVE: Presently, the prone position is necessary for popliteal vein puncture access, but it makes the patients uncomfortable and does not allow traditional femoral or jugular access. To address these deficiencies, this study introduces two new methods, anterior and medial access carried out in the supine position. METHODS: Venous interventions with punctures in the popliteal vein of 120 limbs in 97 patients were performed during the period from February 2017 to April 2019. After puncture, venographic guidance was achieved by dorsal vein injection of contrast medium. Interventional therapy was performed after puncture and insertion of the introducer sheath. RESULTS: In all, 120 limbs were punctured in the popliteal vein, with technical success in 118 (98.3% in total) cases: 100%, 96.1%, and 100% successful punctures in, respectively, 32 anterior, 49 medial, and 37 posterior access cases. A comparison of the three groups revealed that the fluoroscopy time and duration of puncture were longer in the medial and anterior access groups than in the posterior access group. The rate of intra-operative and post-operative complications was 7.5% (9/120), with no statistically significant difference between the three access groups. Compared with the pre-operative median score of 2.5, the post-operative SVS (Society of Vascular Surgery) score of the popliteal vein was reduced to 1.5 in the anterior and 0.5 in the medial groups. CONCLUSION: Medial and anterior puncture of the popliteal vein in the supine position can be used as a safe alternative in venous endovascular therapy. The two new methods can mitigate frailty or respiratory problems resulting from the prone position and facilitate traditional femoral and jugular access.