α-carboline (9H-pyrido[2,3-b]indole), contains a pyridine ring fused with an indole backbone, is a promising scaffold for medicinal chemistry. In recent decades, accumulating evidence shows that α-carboline natural products and their derivatives possess diverse bioactivities. However, hitherto, there is no comprehensive review to systematically summarize this important class of alkaloids. In this perspective, this paper represents the first review to provide a comprehensive description of α-carbolines including natural products, updated literature of synthesis, and their diverse biological activities. Their biological activities including antitumor, anti-microbial, anti-Alzheimer’s disease, anti-atherosclerosis, and antioxidant activities were hilighted. And the targets and the main structure activity relationships (SARs) will be presented. Finally, challenges and future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration for this group of alkaloids.

Background & Aims Lymphocyte-C-reactive Protein Ratio (LCR) has been demonstrated as a promising new marker for predicting surgical and oncological outcomes in colorectal carcinoma (CRC). However, anastomotic leakage (AL) is also likely related to this inflammatory marker. Herein, we aimed to identify preoperative predictors of AL and build and develop a novel model able to identify patients at risk of developing AL. Methods We collected 858 patients with CRC undergoing elective radical operation between 2007 and 2018 at a single center were retrospectively reviewed. We performed univariable and multivariable analyses and built a multivariable model that predicts AL based on preoperative factors. Propensity adjustment was used to correct the bias introduced by non-random matching of the LCR. The model's performance was evaluated by using the area under the receiver operator characteristic curves (AUROCs), decision curve analysis (DCA), Brier scores, D statistics, and R2 values. Results Age, nutrition risk screening 2002 (NRS2002) score, tumor location and LCR, together with hemoglobin < 90 g/l, were independent predictors of AL. The models built on these variables showed good performance (internal validation: c-statistic = 0.851 (95%CI 0.803–0.965), Brier score = 0.049; temporal validation: c-statistic = 0.777 (95%CI 0.823–0.979), Brier score = 0.096). A regression equation to predict the AL was also established by multiple linear regression analysis: [Age(≥ 60 year) × 1.281] + [NRS2002(≥ 3) × 1.341] + [Tumor location(pt.) × 1.348]-[LCR(≤ 6000) × 1.593]-[Hemoglobin(< 90 g/L) × 1.589]-6.12. Conclusion Preoperative LCR is an independent predictive factor for AL. A novel model combining LCR values, age, tumor location, and NRS2002 provided an excellent preoperative prediction of AL in patients with CRC. The nomogram can help clinical decision-making and support future research.

Backgroud Among digestive tract tumors, pancreatic adenocarcinoma (PAAD) has a high degree of malignancy. Therefore, it is important to search for pancreatic adenocarcinoma‐related differential genes and new oncogene therapeutic targets for early diagnosis, treatment, and prognosis of pancreatic adenocarcinoma. Aims This study aims to investigate the expression and clinical significance of Family with sequence similarity 111 member B (FAM111B) in PAAD. Materials & Methods Bioinformatics was used to analyze the relationship between FAM111B expression and pancreatic adenocarcinoma and to predict its role in related pathways. Tissue microarrays were used to assess the levels of FAM111B in pancreatic cancer tissues by immunohistochemical staining, and the effects of FAM111B expression levels on apoptosis, proliferation, invasion and migration of tumor cells were observed and verified by in vitro cellular assays. Results FAM111B expression was higher in PAAD tissue than in matched normal tissues (p < 0.05). The expression level of FAM111B, the metastatic status of lymph nodes was an independent prognostic factor for PAAD survival (p < 0.05). Meanwhile, overexpression of FAM111B promoted PAAD cell proliferation, migration, invasion and inhibited PAAD cell apoptosis (p < 0.05). In contrast, knockdown of FAM111B triggered the opposite result (p < 0.05). In the results of GSEA, it was shown that FAM111B may be involved in PAAD progression through p53 signaling pathway, cell cycle, and other signaling pathways (p < 0.05 and FDR q‐val <0.25). FAM111B is highly expressed in PAAD tissues and is closely associated with poor prognosis of PAAD. Conclusion FAM111B significantly promotes the proliferation, invasion, and migration of pancreatic adenocarcinoma cells while it inhibits their apoptosis. FAM111B may be a new biomarker for PAAD. It may provide a new direction for the treatment and diagnosis of PAAD.

Background: Copper-induced death (cuproptosis) is copper-dependent regulated cell death, which is different from known death mechanisms and is dependent on mitochondrial respiration. However, its effect on breast cancer (BRCA) is unclear. Objective: The objective of this study is to explore the important clinical significance of cuproptosis genes and to provide a new idea for guiding the personalized immunotherapy strategy of BRCA patients. Materials and Method: We collected cuproptosis genes from published work. The gene alteration, differential expression, and prognostic value of cuproptosis genes were explored in BRCA based on TCGA database. We identified two subtypes (clusters A and B) by performing unsupervised clustering. The difference between two clusters was deeply explored, including clinical features, differential expressed genes (DEGs), pathways, and immune cell infiltration. Based on the DEGs between two clusters, a cuproptosis score was constructed and its predictive capability for overall survival of BRCA patients was validated. Results and Discussion: Patients with high cuproptosis score have worse survival status, with an increased infiltration level of most immune cells. Further analysis suggested that BRCA patients with high cuproptosis score may be sensitive to immune checkpoint inhibitor (ICI) treatment. Conclusion: Our findings may improve our understanding of cuproptosis in BRCA and may distinguish patients suitable for ICI treatment. conclusion: Our findings may improve our understanding of cuproptosis in BRCA and may distinguish patients suitable for ICI treatment.

After colonic diverticula, a duodenal diverticulum (DD) is the second most common type of gastrointestinal diverticulum. DD is mainly caused by poor congenital development, resulting in a limited outward protrusion of the duodenal wall in a sac (primary diverticula). Perforation is one of the infrequent but most severe complications of DD, most commonly in the second segment of the duodenum (D2, 58%), followed by the third segment (D3, 30%). In the current case reports on the treatment of DD perforation, preoperative diagnosis is rare, with most patients being diagnosed and treated by laparotomy; the surgical approach is complex and varied, with artificial choices; and there is a high rate of complications and mortality (6%–34%) after surgical treatment. This study aimed to review our experience treating spontaneous perforation of the primary duodenal diverticulum, focusing on the surgical treatment model. A retrospective review of all spontaneous perforations of primary DD was conducted at one center between January 2010 and January 2022. We identified 10 patients with spontaneous perforation of primary DD (6 women and 4 men; median age: 51.5 years; range: 24–87 years). The patients had a median American Society of Anesthesiologists (ASA) score of 2. All patients underwent surgical treatment, of which six had percutaneous retroperitoneal drainage, two had diverticulectomy, one had distal gastrectomy + gastrojejunostomy + diverticuloplasty, and one had diverticulum repair. No patients died. The median length of stay was 12 days (range: 3–21 days). There were no long-term complications during the follow-up period (median follow-up of 12 months). A stepwise treatment model for spontaneous perforation of primary DD appears to have more advantages, and transabdominal exploratory surgery should probably not be the preferred treatment modality.