Constructing a personalized prognostic risk model for colorectal cancer using machine learning and multi-omics approach based on epithelial-mesenchymal transition-related genes.

The progression and the metastatic potential of colorectal cancer (CRC) are intricately linked to the epithelial-mesenchymal transition (EMT) process. The present study harnesses the power of machine learning combined with multi-omics data to develop a risk stratification model anchored on EMT-associated genes. The aim is to facilitate personalized prognostic assessments in CRC. We utilized publicly accessible gene expression datasets to pinpoint EMT-associated genes, employing a CoxBoost algorithm to sift through these genes for prognostic significance. The resultant model, predicated on gene expression levels, underwent rigorous independent validation across various datasets. Our model demonstrated a robust capacity to segregate CRC patients into distinct high- and low-risk categories, each correlating with markedly different survival probabilities. Notably, the risk score emerged as an independent prognostic indicator for CRC. High-risk patients were characterized by an immunosuppressive tumor milieu and a heightened responsiveness to certain chemotherapeutic agents, underlining the model's potential in steering tailored oncological therapies. Moreover, our research unearthed a putative repressive interaction between the long non-coding RNA PVT1 and the EMT-associated genes TIMP1 and MMP1, offering new insights into the molecular intricacies of CRC. In essence, our research introduces a sophisticated risk model, leveraging machine learning and multi-omics insights, which accurately prognosticates outcomes for CRC patients, paving the way for more individualized and effective oncological treatment paradigms.

hsa-miR-7-5p suppresses proliferation, migration and promotes apoptosis in hepatocellular carcinoma cell lines by inhibiting SPC24 expression.

Emerging evidence suggests that microRNAs (miRNAs) participate in hepatocellular carcinoma (HCC) progression. Nevertheless, the mechanism of miR-7-5p in HCC cells has not been researched. In the research, the underlying biological function of miR-7-5p and SPC24 in HCC was explored. qRT-PCR was performed to measure the miR-7-5p and SPC24 level in HCC tissues and cells. The effect of miR-7-5p on HCC progression was detected by performing CCK-8, BrdU, and transwell assay. The relationship between miR-7-5p and SPC24 was determined using luciferase and RNA pull-down assays. Our findings showed that miR-7-5p was downregulated in HCC whereas SPC24 was upregulated in HCC. It was also showed that miR-7-5p upregulation restricted malignant behaviors of HCC cells, but this inhibitory effect of miR-7-5p could be relieved by its target gene SPC24. In conclusion, this research suggested that by inhibiting SPC24, miR-7-5p could act as a tumor inhibitory factor in HCC.

Pancreatic fistula after pancreatoduodenectomy due to compression of the superior mesenteric vessels: a case report.

BACKGROUND: Pancreatic fistula is a common complication after pancreaticoduodenectomy, which could be caused by: soft pancreatic tissue, pancreatic duct diameter < 3 mm and body mass index ≥25 kg/m2. Here we report a case of pancreatic fistula due to obstruction of the jejunal loop due to compression of the jejunal loop by the superior mesenteric vessels. CASE PRESENTATION: A 68-year-old man was admitted to our ward due to intermittent epigastric distension and pain. After various examinations and treatments, he was diagnosed with middle bile duct cancer. Pancreaticoduodenectomy was performed, and pancreaticojejunostomy and hepaticojejunostomy were completed by lifting the jejunal loop from behind the superior mesenteric vessels to the upper region of the colon. On postoperative day 9, the patient developed acute diffuse peritonitis, and on postoperative day 10, the patient underwent a second exploratory laparotomy, during which it was confirmed that the pancreatic fistula was caused by obstruction of the jejunal loop due to compression of the jejunal loop by the superior mesenteric vessels, then the patient recovered and was discharged alive after retrograde drainage in the jejunum. CONCLUSIONS: The superior mesenteric vessels after pancreaticoduodenal surgery can compress the jejunal loop and cause obstruction leading to serious complications, and it is recommended that general surgeons should avoid lifting the jejunal loop from the posterior aspect of the superior mesenteric vessels to complete the anastomosis.

Dietary Sodium Butyrate Improves Intestinal Health of Triploid Oncorhynchus mykiss Fed a Low Fish Meal Diet.

This study aimed to determine the effects of dietary sodium butyrate (NaB) on the growth and gut health of triploid Oncorhynchus mykiss juveniles (8.86 ± 0.36 g) fed a low fish meal diet for 8 weeks, including the inflammatory response, histomorphology, and the composition and functional prediction of microbiota. Five isonitrogenous and isoenergetic practical diets (15.00% fish meal and 21.60% soybean meal) were supplemented with 0.00% (G1), 0.10% (G2), 0.20% (G3), 0.30% (G4), and 0.40% NaB (G5), respectively. After the feeding trial, the mortality for G3 challenged with Aeromonas salmonicida for 7 days was lower than that for G1 and G5. The optimal NaB requirement for triploid O. mykiss based on weight gain rate (WGR) and the specific growth rate (SGR) was estimated to be 0.22% and 0.20%, respectively. The activities of intestinal digestive enzymes increased in fish fed a NaB diet compared to G1 (p < 0.05). G1 also showed obvious signs of inflammation, but this inflammation was significantly alleviated with dietary NaB supplementation. In comparison, G3 exhibited a more complete intestinal mucosal morphology. Dietary 0.20% NaB may play an anti-inflammatory role by inhibiting the NF-κB-P65 inflammatory signaling pathway. Additionally, the relative abundance of probiotics was altered by dietary NaB. In conclusion, dietary 0.20% NaB improved the intestinal health of triploid O. mykiss fed a low fish meal diet.

Effect of dietary phenylalanine on growth performance and intestinal health of triploid rainbow trout (Oncorhynchus mykiss) in low fishmeal diets.

This study aimed to investigate the effects of phenylalanine on the growth, digestive capacity, antioxidant capability, and intestinal health of triploid rainbow trout (Oncorhynchus mykiss) fed a low fish meal diet (15%). Five isonitrogenous and isoenergetic diets with different dietary phenylalanine levels (1.82, 2.03, 2.29, 2.64, and 3.01%) were fed to triplicate groups of 20 fish (initial mean body weight of 36.76 ± 3.13 g). The weight gain rate and specific growth rate were significantly lower (p < 0.05) in the 3.01% group. The trypsin activity in the 2.03% group was significantly higher than that in the control group (p < 0.05). Amylase activity peaked in the 2.64% treatment group. Serum superoxide dismutase, catalase, and lysozyme had the highest values in the 2.03% treatment group. Liver superoxide dismutase and catalase reached their maximum values in the 2.03% treatment group, and lysozyme had the highest value in the 2.29% treatment group. Malondialdehyde levels in both the liver and serum were at their lowest in the 2.29% treatment group. Interleukin factors IL-1ß and IL-6 both reached a minimum in the 2.03% group and were significantly lower than in the control group, while IL-10 reached a maximum in the 2.03% group (p < 0.05). The tight junction protein-related genes occludin, claudin-1, and ZO-1 all attained their highest levels in the 2.03% treatment group and were significantly higher compared to the control group (p < 0.05). The intestinal villi length and muscle layer thickness were also improved in the 2.03% group (p < 0.05). In conclusion, dietary phenylalanine effectively improved the growth, digestion, absorption capacity, antioxidant capacity, and intestinal health of O. mykiss. Using a quadratic curve model analysis based on WGR, the dietary phenylalanine requirement of triploid O. mykiss fed a low fish meal diet (15%) was 2.13%.

Hemolymphangioma of the transverse mesocolon: a case report and literature review.

Hemolymphangioma is an extremely rare type of lymphatic and vascular malformation, histologically comprised of both cystic dilated veins and lymphatic vessels. They have been reported to occur in the skin, extremities, pancreas, spleen, mediastinum, as well as in the gastrointestinal tract. A 61-year-old male patient presented with a 2-week history of left lower abdominal and back pain. He had no relevant personal or family past medical history. He denied fever, trauma or weight change, but had noted early satiety with eating. On physical examination, a 10 cm soft, mobile, well-defined, minimally tender mass was palpated in the lower left abdomen. Computed tomography confirmed a large intraperitoneal cystic mass, and resection was advised. The mass was completely excised laparoscopically from the transverse mesocolon. Histopathology verified the diagnosis of hemolymphangioma. The patient recovered uneventfully, and no recurrence was identified at 3 months follow-up. Hemolymphangioma is more common in women and occurs in the fourth to fifth decades of life. The intent of this case report and literature review was to highlight the key aspects of presentation, organ involvement, imaging, histopathological characteristics, and treatment of hemolymphangioma involving the gastrointestinal tract.

Probiotics Can Boost the Antitumor Immunity of CD8+T Cells in BALB/c Mice and Patients with Colorectal Carcinoma.

BACKGROUND: The drug resistance and the immune suppression in the tumor microenvironment are important factors affecting tumor progression. Reversing drug resistance and changing tumor suppression microenvironment are ideal ways to inhibit tumor progression. OBJECTIVE: The aim of the study is to verify antitumor immune response of probiotics in patients with colorectal carcinoma and to explore its mechanism. METHODS: To detect the tumor samples of 122 patients with colorectal carcinoma after surgery, analyze the effect of probiotics on enhancing tumor-infiltrating CD8+T cells to inhibit colorectal carcinoma, and further verify the mechanism of probiotics on enhancing the antitumor immune response of CD8+T cells through animal experiments. RESULTS: The results of immunohistochemistry showed that the proportion of CD8+T cells in the patients treated with probiotics before surgery was increased significantly than that in other patients (P = 0.033). The results of flow cytometry also showed that the proportion of CD8+T cells in the probiotics group was higher than that in the nonprobiotics group (P = 0.029). Kaplan-Meier survival estimates also showed that the CD8+T cells, TNM stage, pathology grade, lymphatic metastasis, and probiotic treatment were significantly associated with the progression-free survival (PFS) (χ 2 = 9.684, P = 0.002 for CD8+T cells; χ 2 = 5.878, P = 0.015 for TNM stage; χ 2 = 7.398, P = 0.004 for pathology grade; χ 2 = 8.847, P = 0.003 for Lymphatic metastasis; and χ 2 = 4.622, P = 0.032 for the group (group A was treated with probiotics before surgery; group B was not treated with probiotics)). The experimental results in mice showed that probiotics could inhibit tumor growth and increase the proportion of CD8+T cells in mice; the difference was statistically significant (P = 0.037). It was also found that probiotic feeding could upregulate the expression of T-cell immunoglobulin mucin receptor 1(TIM-1) in CD8+T cells of mice and also found that probiotic feeding could downregulate the expression of programmed cell death protein 1 (PD-1) in CD8+T cells of mice, compared with the nonfeeding group; the difference was statistically significant (P = 0.045 for TIM-1 and P = 0.02 for PD-1, respectively). In order to further understand the functional status of CD8+T cells, we analyzed interferon-gamma (IFN-γ)+ T cells and tumor necrosis factor-α (TNF-α)+CD8+T cells by flow cytometry. The results showed that the proportion of IFN-γ + T cells and TNF-α +CD8+T cells significantly increased after probiotic treatment, compared with the nonprobiotic treatment group; the difference was statistically significant (P = 0.040 for IFN-γ + T cells and P = 0.014 for TNF-α +CD8+T, respectively). CONCLUSIONS: Probiotics can enhance the antitumor immune response of CD8+T cells. It can play a synergistic antitumor role. On the one hand, its mechanism is through regulating intestinal flora, and on the other hand, through regulating the antitumor immune function of CD8+T cells.

Sarcopenia as a predictor of poor surgical and oncologic outcomes after abdominal surgery for digestive tract cancer: A prospective cohort study.

BACKGROUND & AIMS: Sarcopenia has been widely recognized as an important predictor of poor outcomes in patients with cancer after surgery, but the controversy remains, and its impact on surgical and oncologic outcomes in patients after abdominal surgery for digestive tract cancer is poorly described. The aim of this study was to evaluate the prognostic impact of sarcopenia on surgical and oncologic outcomes in patients after abdominal surgery for digestive tract cancer. METHODS: Six thousand four hundred and forty-seven consecutive patients who underwent abdominal surgery for digestive tract cancer in our institution were prospectively included. Sarcopenia was defined as skeletal muscle index below the lowest sex-specific quartile using computed tomography scan at L3 before surgery. The surgical and oncologic outcomes were recorded, and univariate and multivariate analyses were performed. RESULTS: Sarcopenia was present in 1638 of 6447 patients (25.4%) with digestive tract cancer before surgery based on the diagnostic cut-off values (43.13 cm2/m2 for men and 37.81 cm2/m2 for women). The incidence of postoperative total and pulmonary complications, and 30-day readmission were significantly higher in sarcopenic group than in nonsarcopenic group (37.4% vs 12.9%, P < 0.001; 3.1% vs 2.1%, P = 0.026; 1.1% vs 0.4%, P = 0.003, respectively). The postoperative hospital stay was significantly longer in sarcopenic patients (9.42 ± 3.40 vs 8.51 ± 3.17 days, P < 0.001). There were significantly more patients receiving postoperative chemotherapy or radiotherapy in sarcopenic group than in nonsarcopenic group (73.1% vs 69.2%, P = 0.003; 10.6% vs 8.8%, P = 0.038, respectively), and patients with sarcopenia had significantly more chemotherapy modifications including delay, dose reduction, or termination (48.5% vs 44.2%, P = 0.018). In addition, during the follow-up period, sarcopenic patients had significantly lower rate of overall survival and disease-free survival than nonsarcopenic patients (53.9% vs 69.3%, P = 0.002; 36.8% vs 59.7%, P = 0.000, respectively). In multivariate analysis, sarcopenia was found to be a risk factor for postoperative complications [odds ratio (OR) = 5.418, 95% confidence interval (CI) = 2.986-9.828, P < 0.001], and was an unfavorable prognostic factor for poor overall survival [hazard ratio (HR) = 0.649, 95% CI = 0.426-0.991, P = 0.045] and disease-free survival (HR = 0.514, 95% CI = 0.348-0.757, P = 0.001). CONCLUSIONS: Sarcopenia could be used as a strong and independent prognostic factor for poor surgical and oncologic outcomes in patients after abdominal surgery for digestive tract cancer. Identification of preoperative sarcopenia in digestive surgery for cancer and targeted approaches may improve its negative outcomes.

Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) as preoperative and postoperative chemotherapy compared with surgery followed by chemotherapy for patients with locally advanced gastric cancer: a propensity score-based analysis.

Introduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC. Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3-4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets. Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218-0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215-3.504) in patients without lymph node metastasis. Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.

The Role of Shcbp1 in Signaling and Disease.

Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and have been shown to play important roles in signaling and disease. Shcbp1 acts as a Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-ß1/Smad and ß -catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphoma, breast cancer, lung cancer, gliomas, synovial sarcoma, human hepatocellular carcinoma and other diseases. Shcbp1 may play an important role in tumorigenesis and progression. Accordingly, recent studies are reviewed herein to discuss and interpret the role of Shcbp1 in normal cell proliferation and differentiation, tumorigenesis and progression, as well as its interactions with proteins.