Identification of Key mRNAs and Pathways in Colorectal Cancer.

Colorectal cancer (CRC) is the third most cancer-related death worldwide. This work aimed to identify potential hub genes and dysregulated pathways in the CRC by bioinformatics analysis. Three gene expression datasets were collected from GEO datasets, including tumor sample (N = 242) and adjacent nontumor tissue sample (N = 59). RankProd was used to discover the differential expressed genes between tumor and adjacent nontumor tissues for datasets generated by different laboratories. The gene set enrichment analysis conducted on the DE genes, followed by the protein-protein interaction (PPI) network. In total, 2,007 significant differential expression (DE) genes between tumor and adjacent nontumor tissues, include 1,090 upregulated genes and 917 downregulated genes in the tumor. The DE mRNAs are involved in cancer-related pathways. We comprehensively identified the CRC-related key mRNAs. Our data demonstrated combined different resources of transcriptomes will promote the understanding of the molecular mechanisms underlying CRC development and may be useful in discovering candidate molecular biomarkers for diagnosing, prognosis, and treating of CRC.

Genome-Wide Network-Based Analysis of Colorectal Cancer Identifies Novel Prognostic Factors and an Integrative Prognostic Index.

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of leading cancers in both incidence and mortality rate. The 5-year survival rate varies considerably depending on the pathological stage of the tumor. Although prominent progress has been made through screening for survival-associated factors from a certain type of genetic or epigenetic modifications, few attempts have been made to apply a network-based approach in prognostic factor identification, which could prove valuable for a complex, multi-faceted disease such as CRC. METHODS: In this study, a TCGA dataset of 379 CRC patients was subjected to a network-based analysis strategy consisting of multivariate regression, co-expression network and gene regulatory network analyses, and survival analyses. Both genetic and epigenetic aberrations, including those in gene expression and DNA methylation at specific sites, were screened for significant association with patient survival. A prognostic index (PI) integrating all potential prognostic factors was subsequently validated for its prognostic value. RESULTS: A collection of six miRNAs, eleven mRNAs, and nine DNA methylation sites were identified as potential prognostic factors. The low- and high-risk patient groups assigned based on PI level showed significant difference in overall survival (hazard ratio = 1.32, 95% confidence interval 1.29-1.36, p < 0.0001). Patients in the low- and high-risk groups can be further divided into a total of four subgroups, based on pathological staging. In the two high-risk subgroups (PI > 0), there was significant different (Cox p < 0.0001) in OS between the earlier (stages I/II) and later stages (stages III/IV). However, in the two low-risk subgroups (PI < 0), earlier (stages I/II) and later stages (stages III/IV) showed no significant difference in OS (Cox p = 0.185). On the other hand, there were significant differences in OS between the low- and high-risk subgroups when both subgroups were of earlier stages (Cox p < 0.001) or of later stages (Cox p < 0.0001). CONCLUSION: The novel network-based, integrative analysis adopted in this study was efficient in screening for prognostic predictors. Along with PI, the set of 6 miRNAs, 11 mRNAs, and 9 DNA methylation sites could serve as the basis for improved prognosis estimation for CRC patients in future clinical practice.

Association between secondhand smoke exposure and rheumatoid arthritis in US never-smoking adults: a cross-sectional study from NHANES.

While smoking is widely acknowledged as a risk factor for rheumatoid arthritis (RA), the connection between secondhand smoke (SHS) exposure and RA in never-smoking adults remains limited and inconsistent. This study aims to explore and quantify this association using serum cotinine levels. We conducted a cross-sectional study with 14,940 adults who self-report as never smokers, using National Health and Nutrition Examination Survey data from 1999 to 2018. Based on previous literature, SHS exposure was categorized into four groups according to serum cotinine levels. Compared to individuals in the unexposed group (serum cotinine < 0.05 ng/mL), the adjusted odds ratio (OR) for RA was 1.37 (95% CI 1.14-1.64, p = 0.001) in the low exposure group (serum cotinine at 0.05 to 0.99 ng/mL) after adjusting for covariates. However, no significant association was found in the moderate exposure group (serum cotinine at 1 to 10 ng/mL) or the heavy exposure group (serum cotinine ≥ 10 ng/mL). Furthermore, we detected a non-linear, positively saturated correlation between the cotinine levels after log2 transformation and RA, with a turning point at approximately - 2.756 ng/mL (OR = 1.163, 95% CI 1.073-1.261, p = 0.0002). The stability of the results was confirmed by subgroup analysis.

Association between metal implants and urinary chromium levels in US adults: a cross-sectional study from NHANES.

Metal implants play a significant role in orthopedics, commonly used for treating fractures, joint replacement surgeries, spinal procedures, and more. Chromium (Cr), crucial in these implants, may raises health concerns. However, the relationship between metal implants and urine Cr levels remains uncertain. We aimed to evaluate this relationship. We conducted a cross-sectional study on 1419 individuals aged 40 years or older using data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2017 to 2020. Multivariate linear regression models and subgroup analysis were applied to assess associations between metal implants and urine Cr levels. Among the 1419 participants, 402 [28.3%] self-reported having metal objects in their bodies. After adjusting for potential confounding factors, metal implants were positively correlated with the accumulation of urine Cr (ß = 0.41, 95% CI 0.04-0.77, p = 0.028). However, the positive correlation of metal implants with urine Cr was only present in females (ß = 0.81, 95% CI 0.08-1.53, p = 0.029), but not in males. Our study revealed higher urine Cr levels in individuals with metal implants, with noticeable gender differences. Additionally, those with metal implants exhibited a more pronounced elevation in urine Cr levels with increasing age compared to individuals without implants.

Meta­analysis of single-incision laparoscopic versus multi-trocar laparoscopic totally extraperitoneal inguinal hernia repair.

Whether single-incision laparoscopic totally extraperitoneal (SIL-TEP) inguinal hernia repair is similar or superior to multi-trocar laparoscopic totally extraperitoneal (MTL-TEP) inguinal hernia repair is controversial. We conducted this meta-analysis to compare the safety, efficacy and cosmetic effect of the two surgical methods. We systematically searched the Cochrane Library, Embase database and PubMed database for published studies on SIL-TEP and MTL-TEP inguinal hernia repair. The studies were screened and evaluated for quality according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for meta-analysis. Twenty studies were included, including 7 randomized controlled studies and 13 nonrandomized controlled studies. Meta-analysis revealed no significant difference between SIL-TEP and MTL-TEP inguinal hernia repair in terms of unilateral operation time (P = 0.12), bilateral operation time (P = 0.72), pain score on the first day after operation (P = 0.61], chronic pain rate (P = 0.61), total complication rate (P = 0.26), hospital stay (P = 0.72), and recurrence rate (P = 0.83), but the cosmetic effect score (P = 0.002) was higher in the former. These findings demonstrate that SIL-TEP inguinal hernia repair is safe, reliable and feasible. In addition, it can result in a better cosmetic effect of the incision than MTL-TEP inguinal hernia repair. SIL-TEP inguinal hernia repair should be considered for patients with stricter cosmetic requirements.Clinical trial registration: INPLASY2022110085.

Driving risk cognition of passengers in highly automated driving based on the prefrontal cortex activity via fNIRS.

For high-level automated vehicles, the human being acts as the passenger instead of the driver and does not need to operate vehicles, it makes the brain-computer interface system of high-level automated vehicles depend on the brain state of passengers rather than that of drivers. Particularly when confronting challenging driving situations, how to implement the mental states of passengers into safe driving is a vital choice in the future. Quantifying the cognition of the driving risk of the passenger is a basic step in achieving this goal. In this paper, the passengers' mental activities in low-risk episode and high-risk episode were compared, the influences on passengers' mental activities caused by driving scenario risk was first explored via fNIRS. The results showed that the mental activities of passengers caused by driving scenario risk in the Brodmann area 10 are very active, which was verified by examining the real-driving data collected in corresponding challenging experiments, and there is a positive correlation between the cerebral oxygen and the driving risk field. This initial finding provides a possible solution to design a human-centred intelligent system to promise safe driving for high-level automated vehicles using passengers' driving risk cognition.

TRPV1 Induced Apoptosis of Colorectal Cancer Cells by Activating Calcineurin-NFAT2-p53 Signaling Pathway.

BACKGROUND/AIMS: TRPV1 is a nonselective Ca2+ channel which has recently been observed in many cancers, while its effect on cell proliferation, apoptosis, metabolism, and cancer development in colorectal cancer (CRC) is still unclear. In this study, we hypothesized that TRPV1 is a tumor suppressor in CRC development as well as the underlying mechanism. METHODS: Immunohistochemistry assay was applied to detect the expression of TRPV1 protein in CRC tissues. HCT116 cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. Cellular Ca2+ concentration was measured by Fluo-4/AM-based flow cytometer. Apoptosis-related proteins were measured by Western blotting. RESULTS: In this study, we found that TRPV1 expression was significantly decreased in CRC tissues, compared with CRC-adjacent tissues and normal tissues, respectively. Then, we found that the TRVP1 agonist capsaicin treatment inhibited CRC growth and induced apoptosis by activating P53. Subsequent mechanistic study revealed that the TRPV1 induced cytosolic Ca2+ influx to regulate cell apoptosis and p53 activation through calcineurin. CONCLUSIONS: This study suggests that TRPV1 served as a tumor suppressor in CRC and contributed to the development of novel therapy of CRC.

A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review.

Familial adenomatous polyposis (FAP), an autosomal dominant disease, is a colon cancer predisposition syndrome that manifests as a large number of adenomatous polyps. Mutations in the Adenomatous polyposis coli (APC) gene are responsible for the majority of cases of FAP. The purpose of the present study was to report the clinical features of a Chinese family with FAP and screen for novel mutations using the targeted next­generation sequencing technology. Among the 29 family members, 12 were diagnosed of FAP. Based on an established filtering strategy and data analyses, along with confirmation by Sanger sequencing and co­segregation, a novel frameshift mutation c.1317delA (p.Ala440LeufsTer14) in exon 10 of the APC gene was identified. To the best of our knowledge, this mutation has not been reported prior to the present study. In addition, it was correlated with extra­colonic phenotypes featuring duodenal polyposis and sebaceous cysts in this family. This novel frameshift mutation causing FAP not only expands the germline mutation spectrum of the APC gene in the Chinese population, but it also increases the understanding of the phenotypic and genotypic correlations of FAP, and may potentially lead to improved genetic counseling and specific treatment for families with FAP in the future.