Construction and Validation of a Gastric Cancer Diagnostic Model based on Blood Groups and Tumor Markers.

Objective: The aim of this study is to explore the value of combined detection of ABO blood group and tumor markers in the diagnosis of gastric cancer. Methods: A total of 3650 gastric cancer patients treated in our center from January 2015 to December 2019, and 5822 controls were recruited, and divided into training set and validation set according to 7:3. The diagnostic and predictive model of gastric cancer was constructed by binary logistic regression method in the training set. The diagnostic value of the prediction model for gastric cancer was evaluated by calculating the prediction probability P value and drawing the Receiver operating characteristic (ROC) curve, and was verified in the validation set. Results: The Area under the curve (AUC) of the diagnosis and prediction model in the training set was 0.936 (95%CI: 0.926-0.941), the sensitivity was 81.66%, and the specificity was 98.61%. In the validation set, the AUC was 0.941 (95%CI: 0.932-0.950), the sensitivity was 82.33%, and the specificity was 99.02%. Furthermore, the diagnostic model obtained in this study had a high diagnostic value for early gastric cancer patients in the healthy population (AUC of training set, validation set and total population were 0.906, 0.920 and 0.908, respectively). Conclusions: We constructed a diagnostic model for gastric cancer including blood group and tumor markers, which has high reference value for the diagnosis of gastric cancer patients, and the model can better distinguish early gastric cancer from healthy people.

Expression and significance of CDX2, FXR, and TGR5 in esophageal cancer.

This study explored the expression and significance of three critical morphogenesis genes in normal esophagus, reflux esophagitis (RE), Barrett's esophagus (BE), esophageal adenocarcinoma (EA), and esophageal squamous cell carcinoma (ESCC). Esophageal tissue samples and tissue microarrays were used. CDX2, FXR, and TGR5 protein expression were measured by immunohistochemistry in normal esophageal, RE, BE, EA, and ESCC tissues. All 3 proteins had markedly changed expression during the progression of EA. The expressions of CDX2 and FXR were positively correlated in EA. In addition, TGR5 expression was positively correlated with CDX2 in RE and BE. The expressions of CDX2 and FXR were also positively correlated in ESCC. Although CDX2, FXR, and TGR5 were upregulated in ESCC, these factors might not be markers for the prognosis of ESCC. These results suggested that CDX2, FXR, and TGR5 might play different roles in EA and ESCC. They may represent novel therapeutic targets for patients with these cancers.

m6A-Related Angiogenic Genes to Construct Prognostic Signature, Reveal Immune and Oxidative Stress Landscape, and Screen Drugs in Hepatocellular Carcinoma.

Background: m6A modification plays a key role in the development of hepatocellular carcinoma (HCC). Angiogenesis-related genes (ARGs) are increasingly being used to define signatures predicting patient prognosis. The correlations between m6A-related ARGs (mARGs), clinical outcomes, and the immune and oxidative stress landscape are unclear. Methods: Univariate Cox regression analysis of 24 mARGs yielded 13 prognostic genes, which were then analyzed for their enriched functions and pathways. After LASSO regression analysis, a prognostic signature was constructed and its reliability validated. Patients were grouped by risk using the signature score, and then the clinical prognosis, the immune landscape, and the oxidative stress landscape between the two groups were analyzed. Drug sensitivity analysis was performed to identify potentially efficient therapeutic agents. Results: Thirteen prognosis-related mARGs consistently clustered patients with HCC into four groups with significantly different prognosis. Four mARGs (EGF, ITGA5, ITGAV, and PLG) were used to construct a prognostic signature and define risk groups. Among them, EGF, ITGA5, and ITGAV, were defined as prognostic risk factors, while PLG was defined as a prognostic protective factor. Compared to low-risk patients, HCC patients in the high-risk group had a poorer prognosis and showed significant differences in clinical characteristics, enriched pathways, tumor stemness, and tumor microenvironment. The drug sensitivity of oxaliplatin and LDK-378 negatively correlated with ITGAV expression. Ten drugs had lower IC50s in the high-risk group, indicating better antitumor efficacy than in the low-risk group, with epothilone B having the lowest IC50 value. Conclusions: A prognostic model consisting of mARGs can be used to predict the prognosis of HCC patients. The risk grouping of our model can be used to reveal differences in the tumor immune microenvironment of patients with HCC. Further in-depth study may provide new targets for future treatment.

M2-like tumor-associated macrophage-related biomarkers to construct a novel prognostic signature, reveal the immune landscape, and screen drugs in hepatocellular carcinoma.

Background: M2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the "immune landscape", and screen drugs in HCC. Methods: M2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene-drug correlation and sensitivity to anti-cancer drugs were conducted. Results: A total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested. Conclusions: Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

Bile reflux and bile acids in the progression of gastric intestinal metaplasia.

ABSTRACT: Gastric intestinal metaplasia (GIM) is a precancerous lesion of gastric cancer (GC) and is considered an irreversible point of progression for GC. Helicobacter pylori infection can cause GIM, but its eradication still does not reverse the process. Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa, and bile acids in refluxed fluid have been widely reported to be associated with GIM. This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM.

The clinicopathological characteristics of early-onset gastric cancer and its evolutionary trends: a retrospective study.

Although gastric cancer (GC) is most common in the elderly population, the rate of early-onset gastric cancer (EOGC) is increasing each year. In this study, the clinicopathological information of 9,406 patients who underwent GC resection in our institution from 2000 to 2019 was collected. We compared the clinicopathological characteristics between the EOGC group, in which patients were younger than 40, and the control group, summarizing the evolutionary trends of the EOGC group's characteristics. Then, we focused on the characteristics of EOGC in different sex groups and the evolutionary trends of female EOGC patients' clinicopathological characteristics. The results showed that a greater proportion of the EOGC group was female (47.32% vs. 23.53%), had poorly differentiated adenocarcinoma (84.78% vs. 64.11%), gastric antrum cancer (59.38% vs. 50.72%) and signet ring cell carcinoma (21.13% vs. 8.51%). Over the past 20 years, the proportion of EOGC patients with T4 stage (10.71% to 41.74%), N3 stage (0 to 30.73%) and poorly differentiated adenocarcinoma (70.37% to 92.23%) has increased. In the female EOGC group, there were more patients with stage III-IV disease (57.23% vs. 43.22%), T4 stage (35.85% vs. 22.60%), and poorly differentiated adenocarcinoma (91.88% vs. 78.68%). Additionally, the proportions of T4 stage (16.13% to 50.50%), N3 stage (0% to 31.68%), and poorly differentiated adenocarcinoma (69.23% to 98.97%) gradually increased. In conclusion, our study not only identified unique clinicopathological characteristics of EOGC but also revealed the evolutionary trends of these indicators, which may provide some theoretical basis for the prevention and diagnosis of EOGC.

Serum Total Bile Acids in Relation to Gastrointestinal Cancer Risk: A Retrospective Study.

Background: Bile acids (BAs) have been proposed to promote gastrointestinal cells carcinogenesis. However, studies on serum total bile acid (TBA) levels and gastrointestinal cancers (GICs) risk are rare. Methods: We conducted a retrospective case-control study from 2015 to 2019 at the First Affiliated Hospital of Air Force Military Medical University, in which 4,256 GICs cases and 1,333 controls were recruited. Patients' demographic, clinical and laboratory data were collected. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using binary logistic regression models. Results: Positive associations were observed between serum TBA levels and risks of esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC). Overall, ORs of EC, GC and CRC risk rose with the TBA levels increasing. After adjustment for potential confounders, the OR of TBA-positive for EC risk was 4.89 (95% CI: 3.20-7.49), followed by GC (OR: 3.92, 95% CI: 2.53-6.08), and CRC (OR: 3.32, 95% CI: 2.04-5.11). Patients aged 60 years or older have a higher risk of GICs, especially for EC patients. Males are associated with a higher risk of GC, while females are associated with a higher risk of CRC. Preoperative serum TBA positive and negative was significantly different in the presence or absence of hematogenous metastasis among EC patients (P=0.014), and lymph node metastasis among GC patients (P=0.018). Conclusions: This retrospective study showed positive associations between serum TBA level and GICs risk, and a higher serum TBA level constitutes a risk factor for GICs.

[Temporal-spatial distribution and ecological evaluation of macroinvertebrate functional feeding groups in Yongding River Basin]. / æ°¸å®šæ²³æµåŸŸå¤§åž‹åº•æ –åŠ¨ç‰©åŠŸèƒ½æ‘„é£Ÿç±»ç¾¤æ—¶ç©ºåˆ†å¸ƒåŠç”Ÿæ€è¯„ä»·.

We investigated community structure of macroinvertebrate, water environment factors, hydrological factors at 23 sampling sites of the Yongding River basin from spring 2017 (April) to autumn 2017 (November). We analyzed the composition, spatial and temporal distribution of the macroinvertebrate functional feeding groups, as well as their responses to changes in riverine habitat. A total of 78 macroinvertebrate species were identified, with 52, 50 and 53 macroinvertebrate species in spring, summer and autumn respectively. The dominant functional feeding groups were gather-collectors, followed by predators, while the proportion of scrapers, filter-collectors and shredders were extremely low. Dominant species in the three seasons were all gather-collectors, including Orthocladius, Rheotanytarsus, Cricotopus in spring, Glyptotendipes in summer, and Polypedilum, Chironomus, Orthocladius in autumn. Results of redundancy analysis showed that the functional feeding groups of macroinvertebrate community structure were mainly influenced by water temperature, flow velocity, salinity, and total phosphorus in spring, by total phosphorus, dissolved oxygen, conductivity and flow capacity in summer, and by total phosphorus and dissolved oxygen in autumn. Total phosphorus had positive correlation with gather-collectors in all three seasons, indicating that the functional feeding groups of macroinvertebrates were affected by water pollution. The evaluation based on the metrics of functional feeding groups showed that: 1) in terms of material cycle, primary productivity of Guishui River were significantly higher than other regions, and that in autumn were significantly higher than other seasons. The secondary productivity and decomposition capacity of Yanghe River were significantly higher than other regions, and those in spring were significantly higher than other seasons. The autotrophy/heterotrophy of Yanghe River was significantly lower than other regions, and that in spring were significantly higher than other seasons. 2) The longitudinal transport capacity of Sanggan River was significantly higher than other regions, and that in autumn was significantly higher than other seasons. 3) The lateral input capacity of Guishui River was significantly higher than other regions, and that in summer was significantly higher than other seasons.

[Distribution pattern of macroinvertebrate community and its relationships with environmental factors in the Yongding River Basin]. / æ°¸å®šæ²³æµåŸŸå¤§åž‹åº•æ –åŠ¨ç‰©ç¾¤è½åˆ†å¸ƒæ ¼å±€åŠå ¶å½±å“å› å­.

Human disturbances have altered global stream ecosystems in multiple ways. Understan-ding spatio-temporal dynamics of aquatic organism composition and their relationships with environmental factors play an important role in revealing changes in the structure and function of river ecosystems. The macroinvertebrates and environmental parameters were sampled in the Yongding River Basin at spring (March), summer (July), and autumn (November) in 2017. The results showed that chironomids were the dominant group in the Yongding River Basin, including Orthocladius, Chironomus, Glyptotendipes, and Polypedilum. Results of the cluster analysis showed significant spatial variations of macroinvertebrate community. Sampling sites were clustered into two groups based on the similarities of macroinvertebrate composition in the Yongding River. Sampling sites belonging to group 1 mainly located in the Sanggan River and Dongyang River, with Orthocladius sp.being the dominant species. Sampling sites belonging to group 2 mainly located in the Yang River, Guishui River and main section of the Yongding River, with Glyptotendipes sp. being the dominant species. The biomass, Shannon index, Margalef index, Pielou evenness index and taxa richness of group 2 were significantly higher than those of group 1. Higher values of biological indices indicated better ecological condition of the stream ecosystem. The density, biomass and diversity indices of summer were significantly lower than those of both spring and autumn. Results of Canonical correspondence analysis (CCA) showed that the spatio-temporal distribution of macroinvertebrate in the Yongding River was mainly influenced by water temperature, ammonium, pH, dissolved oxygen, and total phosphorus. From the perspective of hydrological characteristics, flow velocity and flow capacity were significantly correlated. The significant positive correlations between hydrological parameters of velocity and capacity and biological indices of density and EPT% in group 2 indicated the preference of fast flow to sensitive taxa of EPT (Ephemeroptera, Plecoptera, and Trichoptera). The negative correlations between flow capacity and biodiversity indices implied the adverse effects of high flow on macroinvertebrate biodiversity. Our results confirmed that the composition and biodiversity of macroinvertebrate were affected by both water environment and hydrology, which reflected the multiple human activities in aquatic ecosystems of the Yongding River. It is important to control water contamination and sustain environmental flow at the specific reaches for the restoration of Yongding River.