Cdx2 is a homeobox domain-containing transcription factor that is important in the development and differentiation of the intestinal cells, and served as a potential biomarker of tumor progression in early intestinal-type gastric cancer. However, its prognostic value and significance in gastric cancer remain controversial. A meta-analysis based on published studies was performed to obtain an accurate evaluation of the association between the presence of Cdx2-positive in clinical samples and clinical outcome. A total of 13 eligible retrospective cohort studies with 1513 patients were included. Cdx2-positive cases were significantly associated with higher male-to-female ratio (RR=1.27, 95% CI: 1.17–1.38, P<0.00001 fixed-effect), lower (I+II) clinical stage (RR=1.63, 95% CI: 1.42–1.87, P<0.00001 fixed-effect), better histologic differentiation (RR=1.54, 95% CI: 1.34-1.76, P<0.00001 fixed-effect), and lower rate of vascular invasion (RR=1.23, 95% CI: 1.08-1.41, P=0.002 fixed-effect) and lymph node metastasis (RR=1.52, 95% CI: 1.33-1.73, P<0.00001 fixed-effect), as well as higher 5-year survival rate (HR=2.22, 95% CI: 1.78-2.75, P<0.00001 fixed-effect). However, the presence of Cdx2 was not associated with tumor size. In summary, Cdx2 is a prognostic factor in gastric cancer, which acts as a marker of good outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of Cdx2 in clinical practice.

In lower rectal cancer, postoperative outcome is still subject of controversy between the advocates of abdominoperineal resection (APR) and low anterior resection (LAR). Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. Publications were identified which assessed the differences comparing 5-year survival, local recurrence, circumferential resection margin rate, complications and so on. A meta-analysis was performed to clarify the safety and feasibility of the two procedures with several types of outcome measures. A total of 13 studies met the inclusion criteria, and comprised 6,850 cases. Analysis of these data showed that LAR group was highly correlated with 5-year survival (pooled OR = 1.73, 95%CI: 1.30–2.29, P = 0.0002 random-effect). And local recurrence rate of APR group was significantly higher than that in LAR group (pooled OR = 0.63, 95%CI: 0.53–0.75, P < 0.00001 fixed-effect). Also, the circumferential resection margin (CRM) were high involved in APR group than in LAR group. (5 trials reported the data, pooled OR = 0.43, 95%CI: 0.36–0.52, P < 0.00001 fixed-effect). Besides, the incidents of overall complications of APR group was higher compared with LAR group (pooled OR = 0.52, 95%CI: 0.29–0.92, P = 0.03 random-effect). Patients treated by APR have a higher rate of CRM involvement, a higher local recurrence, and poorer prognosis than LAR. And there is evidence that in selected low rectal cancer patients, LAR can be used safely with a better oncological outcome than APR. due to the inherent limitations of the present study, for example, the trails available for this systematic review are limited and the finite retrospective data, future prospective randomized controlled trials will be useful to fully investigate these outcome measures and to confirm this conclusion.

This research investigates the causal relationships among gut microbiota, inflammatory proteins, and inflammatory bowel disease (IBD), including crohn disease (CD) and ulcerative colitis (UC), and identifies the role of inflammatory proteins as potential mediators. Our study analyzed gut microbiome data from 13,266 samples collected by the MiBioGen alliance, along with inflammatory protein data from recent research by Zhao et al, and genetic data on CD and UC from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We used Mendelian randomization (MR) to explore the associations, complemented by replication, meta-analysis, and multivariable MR techniques for enhanced accuracy and robustness. Our analysis employed several statistical methods, including inverse-variance weighting, MR-Egger, and the weighted median method, ensuring comprehensive and precise evaluation. After MR analysis, replication and meta-analysis, we revealed significant associations between 11 types of gut microbiota and 17 inflammatory proteins were associated with CD and UC. Mediator MR analysis and multivariable MR analysis showed that in CD, the CD40L receptor mediated the causal effect of Defluviitaleaceae UCG-011 on CD (mediation ratio 8.3%), and the Hepatocyte growth factor mediated the causal effect of Odoribacter on CD (mediation ratio 18%). In UC, the C-C motif chemokine 4 mediated the causal effect of Ruminococcus2 on UC (mediation ratio 4%). This research demonstrates the interactions between specific gut microbiota, inflammatory proteins, and CD and UC. Furthermore, the CD40L receptor may mediate the relationship between Defluviitaleaceae UCG-011 and CD; the Hepatocyte growth factor may mediate the relationship between Odoribacter and CD; and the C-C motif chemokine 4 may mediate the relationship between Ruminococcus2 and UC. The identified associations and mediation effects offer insights into potential therapeutic approaches targeting the gut microbiome for managing CD and UC.

Siva‑1 is a well‑known anti‑apoptosis protein that serves a role in multiple types of cancer cells. However, whether Siva‑1 affects multidrug resistance via the NF‑κB pathway in gastric cancer is currently unknown. The present study aimed to determine the possible involvement of Siva‑1 in gastric cancer anticancer drug resistance in vitro. A vincristine (VCR)‑resistant KATO III/VCR gastric cancer cell line with stable Siva‑1 overexpression was established. The protein expression levels of Siva‑1, NF‑κB, multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1) were detected via western blotting. The effect of Siva‑1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5‑fluorouracil and doxorubicin. The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. Additionally, colony formation, wound healing and Transwell assays were used to detect the proliferation, migration and invasion of cells, respectively. The results of the current study revealed that the Siva‑1‑overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5‑fluorouracil and doxorubicin. The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva‑1. The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva‑1 overexpression. Additionally, Siva‑1 overexpression increased the migration and invasion of KATO III/VCR cells in vitro. Western blot analysis determined that Siva‑1 overexpression increased NF‑κB, MDR1 and MRP1 levels. The current study demonstrated that overexpression of Siva‑1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells via promotion of NF‑κB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. These data provided novel insight into the molecular mechanisms of gastric cancer, and may be of significance for the clinical diagnosis and therapy of patients with gastric cancer.

Introduction: Siva-1, as a pro-apoptotic protein, has been shown to induce extensive apoptosis in a number of different cell lines. In our previous study, we showed that overexpressed Siva-1 decreased the apoptosis of gastric cancer cells. So, we believe that it can also work as an anti-apoptotic protein. The present study aimed to determine the specific role of Siva-1 in anticancer drug resistance in gastric cancer in vivo and in vitro and preliminarily reveal the mechanism. Materials and Methods: A vincristine-resistant MKN-28/VCR gastric cancer cell line with stably downregulated Siva-1 was established. The effect of Siva-1 downregulation on chemotherapeutic drug resistance was assessed by measuring the IC50 and pump rate of doxorubicin. Proliferation, apoptosis of cells, and cell cycle were detected via colony formation assay and flow cytometry, respectively. Additionally, migration and invasion of cells was detected via wound healing and transwell assays. Moreover, we determined in vivo effects of LV-Siva-1-RNAi on tumor size, and apoptotic cells in tumor tissues were detected using TUNEL and hematoxylin and eosin staining. Results: Siva-1 downregulation reduced the pump rate of doxorubicin and enhanced the response to drug treatment. Siva-1 negatively regulated proliferation and promoted apoptosis of cells by potentiality G2-M phase arresting. Inhibition of Siva-1 expression in MKN-28/VCR cells significantly weakened wound healing ability and decreased invasion ability. Poly(C)-binding protein 1 (PCBP1) was identified as a Siva-1-interacting protein in yeast two-hybrid screening. Semiquantitative RTPCR and western blotting revealed that Siva-1 downregulation could inhibit expression of PCBP1, Akt, and NF-κB and eventually decrease the expression of MDR1 and MRP1. Conclusion: The current study demonstrated that the downregulation of Siva-1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells by inhibiting PCBP1/Akt/NF-κB signaling pathway expression, enhanced the sensitivity of gastric cancer cells to certain chemotherapies.

Background: SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance in vitro. Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear.