Background: Limited evidence exists on the incidence of gastric cancer (GC), and contradictory results exist for the prognosis of GC based on the Lauren classification. We analyzed the incidence and survival of GC based on the Lauren classification. Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2015 was used to identify all patients with surgically resected, histologically diagnosed intestinal or diffused-type GC. Propensity score matching was used to analyze the association between the Lauren classification type and prognosis. Results: The trend of total GC incidence showed an obvious decrease (APC = −1.51, 95% CI: −2.31 to −1.01) as well as that of the intestinal type (APC = −1.43, 95% CI: −2.01 to −1.12). However, we found that the relative incidence of the diffused type was increased (APC = 0.6, 95% CI: 0.41–0.82). The trend of the total incidence of GC (APC = −1.31, 95% CI: −1.91 to −1.03) and that of the intestinal type (APC = −1.11, 95% CI: −1.53 to −0.98) was decreased in 40–49-year-olds, but that of the diffused type was increased (APC = 1.5, 95% CI: 1.2–1.72). We found that trends in GC incidence exhibited a similar pattern in the regional and distant stages and showed a decrease from 1975 through 2015. However, the incidence rate of the local stage was increased, with an APC of 0.5 (95% CI: 0.3–0.7). We identified 15,989 GC cases from the SEER database, including 13,852 intestinal-type and 2,138 diffused-type cases. The 1,336 intestinal-type cases were matched with 1,336 diffused-type cases using propensity score matching (PSM), and patients with the diffused type had a better prognosis than patients with the intestinal type (HR = 0.56, 95% CI: 0.45–0.78). However, we found that patients with diffused-type GC had worse survival than patients with intestinal-type GC in the cohort from Renji Hospital (P < 0.001). Conclusion: The total incidence of GC and that of the intestinal-type GC decreased, but the incidence of diffused-type GC increased in 40–49-year-olds. Diffused types of GCs may have a different prognosis compared to intestinal-type GCs in different patient cohorts. Nevertheless, these results should be interpreted with caution in assessing the prognosis in combination with other factors.

Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that taraxasterol acetate (TA) can inhibit the growth of tumor cells. However, to date, it remains unclear how TA inhibits cell growth and how RNF31 functions as an oncogene. We examined the expression of RNF31 in CRC tissue samples via immunohistochemistry and elucidated the function of RNF31 in CRC cells by constructing a cell model with RNF31 depletion. A cycloheximide (CHX)-chase analysis and immunofluorescence assays were conducted to demonstrate that TA can promote RNF31 degradation by activating autophagy. We used the PharmMapper website to predict targets of TA and identified RNF31. CHX-chase experiments showed that TA could facilitate RNF31 degradation, which was inhibited by the administration of chloroquine. Immunofluorescence assays showed that RNF31 protein was colocalized with LC3I/II and p62, suggesting that TA promoted RNF31 degradation by activating autophagy. We also found that CRC patients with RNF31 overexpression had poorer survival than those with low RNF31 expression. The results of the CHX-chase experiment showed that depletion of RNF31 alleviated p53 degradation, which was inhibited by MG132. A series of co-immunoprecipitation (Co-IP) assays revealed that RNF31 interacts with p53 and promotes p53 ubiquitination and degradation. A Co-IP assay performed with a truncated RNF31 plasmid showed that the PUB domain interacts with p53. Moreover, the PUB domain is the key structure in the induction of p53 ubiquitination. Our findings reveal a key role of RNF31 in CRC cell growth and indicate a mechanism through which TA inhibits cell growth.

Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC using network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are very important to the PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had a good binding ability with the Hub gene. This study systematically elucidates the “multi-component, multi-target, multi-pathway” mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

Background: Limited evidence and contradictory results have been reported regarding the impact of signet ring cell carcinoma (SRC) and mucinous gastric cancer (MGC) classifications on the prognosis of gastric cancer (GC). Results: Information on 6017 patients and 266 patients was extracted from the SEER database and our hospital records, respectively. We found that patients with MGC had a better survival rate than those with SRC (P=0.012), but in the early stage, MGC was a risk factor for a poor prognosis. After PSM, for both patients from the SEER database and our hospital, the prognosis of patients with SRC was poorer than that of patients with MGC (P<0.05), but patients with MGC in early-stage GC showed poorer survival. Additionally, SRC was demonstrated to be a risk factor in the multivariate competing risk regression model for cancer-specific survival. Conclusion: Patients with SRC may have a worse prognosis than those with MGC, but for early-stage GC, patients with SRC have a better prognosis than those with MGC. Method: Patients from the SEER database and from our hospital diagnosed with SRC or MGC were included in a Cox regression analysis, multivariate competing risk model and propensity score matching (PSM) analysis.

Chronic colorectal inflammation has been associated with colorectal cancer (CRC); however, its exact molecular mechanisms remain unclear. The present study aimed to investigate the effect of Toll‑like receptor 9 (TLR9) on the development of colitis‑associated CRC (CAC) through its regulation of the NF‑κB signaling pathway. By using a CAC mouse model and immunohistochemistry, the present study discovered that the protein expression levels of TLR9 were gradually upregulated during the development of CRC. In addition, the expression levels of TLR9 were revealed to be positively correlated with NF‑κB and Ki67 expression levels. In vitro, inhibiting TLR9 expression levels using chloroquine decreased the cell viability, proliferation and migration of the CRC cell line HT29, and further experiments indicated that this may occur through downregulating the expression levels of NF‑κB, proliferating cell nuclear antigen and Bcl‑xl. In conclusion, the findings of the present study suggested that TLR9 may serve an important role in the development of CAC by regulating NF‑κB signaling.