Activating transcription factor 4 (ATF4) is a DNA-binding protein widely generated in mammals, which has two biological characteristics that bind the cAMP response element (CRE). The mechanism of ATF4 as a transcription factor in gastric cancer affecting the Hedgehog pathway remains unclear. Here, we observed that ATF4 was markedly upregulated in gastric cancer (GC) using immunohistochemistry and Western blotting assays in 80 paraffin-embedded GC samples and 4 fresh samples and para-cancerous tissues. ATF4 knockdown using lentiviral vectors strongly inhibited the proliferation and invasion of GC cells. ATF4 upregulation using lentiviral vectors promoted the proliferation and invasion of GC cells. We predicted that the transcription factor ATF4 is bound to the SHH promoter via the JASPA database. Transcription factor ATF4 is bound to the promoter region of SHH to activate the Sonic Hedgehog pathway. Mechanistically, rescue assays showed that ATF4 regulated gastric cancer cells’ proliferation and invasive ability through SHH. Similarly, ATF4 enhanced the tumor formation of GC cells in a xenograft model.

Background: Currently, there is no consensus on the most appropriate anastomotic site, anastomotic line, and direction for Billroth-II reconstruction with Braun anastomosis (B-II-B anastomosis) during totally laparoscopic distal gastrectomy (TLDG). Herein, the authors presented a novel anastomotic technique called R anastomosis for B-II-B anastomosis and compared it with the conventional B-II-B anastomosis technique to assess its feasibility, safety, and effectiveness. Methods: Between March 2019 and September 2022 in our centre, R anastomosis was performed on 123 patients undergoing TLDG for distal gastric cancer. A retrospective review of a prospectively collected database identified patients who underwent TLDG between January 2010 and September 2022. Patients who underwent R anastomosis were matched in a 1:1 ratio with patients who underwent conventional anastomosis using a propensity score based on age, sex, preoperative BMI, American Society of Anesthesiologists (ASA) score, and the history of abdominal surgery. Surgical and postoperative outcomes and clinicopathological data were analyzed for both groups. Results: During the study period, 246 patients were included, 123 in each group. No intraoperative complications associated with digestive tract reconstruction and no cases of conversion to open surgery were reported in either group; furthermore, no incidences of perioperative mortality were noted in either group. The R group had a significantly reduced anastomotic time compared to the control group (30 ± 4.1 vs. 36 ± 5.3 min, P < 0.001). Perioperatively, the incidences of Clavien–Dindo grade II or higher complications were 6.5% (8/123) and 12.2% (15/123) in the R and control groups with no significant difference between the two groups. Postoperative gastric emptying dysfunction was found in five and one patient in the control and R groups, respectively. Conclusion: R anastomosis is a safe and effective technique for B-II-B anastomosis following TLDG. This novel technique enhances the convenience of performing anastomosis and can reduce postoperative gastric emptying dysfunction.

Background The protein meflin encoded by ISLR contains a C2-type immunoglobulin (Ig)-like domain and five leucine-rich repeat (LRR) domains. ISLR is known to play a role in a small number of tumors, but its role in most tumors is unknown. The purpose of this study was to analyze the expression and prognosis of ISLR in pan-cancer, as well as its correlation with tumor immunity. Methods We used multiple databases and R software to conduct bioinformatics analysis to explore the predictive role of ISLR in pan-cancer, mainly involving expression patterns, prognosis, and immune infiltration. Results Compared with normal tissues, the expression of ISLR was significantly increased or decreased in most tumors. Moreover, the high expression of ISLR may cause the prognosis of some tumors to become better or worse. ISLR also affects immune infiltration in a variety of tumors, which affects the clinical prognosis. ISLR is also significantly related to TMB and MSI in pan-cancer and is related to genes encoding immune regulatory genes. ISLR also affects various cancer-and immune-related pathways. Conclusions ISLR is differentially expressed in tumors, may regulate TME, affect tumor prognosis, and is expected to become a prognostic biomarker.