Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases.

BACKGROUND: Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes. AIM: To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment. METHODS: Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort. RESULTS: A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit. CONCLUSION: Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

Clinical efficacy of total laparoscopic splenectomy for portal hypertension and its influence on hepatic hemodynamics and liver function.

BACKGROUND: The liver hemodynamic changes caused by portal hypertension (PH) are closely related to various complications such as gastroesophageal varices and portosys-temic shunts, which may lead to adverse clinical outcomes in these patients, so it is of great clinical significance to find treatment strategies with favorable clinical efficacy and low risk of complications. AIM: To study the clinical efficacy of total laparoscopic splenectomy (TLS) for PH and its influence on hepatic hemodynamics and liver function. METHODS: Among the 199 PH patients selected from October 2016 to October 2020, 100 patients [observation group (OG)] were treated with TLS, while the remaining 99 [reference group (RG)] were treated with open splenectomy (OS). We observed and compared the clinical efficacy, operation indexes [operative time (OT) and intraoperative bleeding volume], safety (intraperitoneal hemorrhage, ascitic fluid infection, eating disorders, liver insufficiency, and perioperative death), hepatic hemodynamics (diameter, velocity, and flow volume of the portal vein system), and liver function [serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and serum total bilirubin (TBil)] of the two groups. RESULTS: The OT was significantly longer and intraoperative bleeding volume was significantly lesser in the OG than in the RG. Additionally, the overall response rate, postoperative complications rate, and liver function indexes (ALT, AST, and TBil) did not differ significantly between the OG and RG. The hepatic hemodynamics statistics showed that the pre- and postoperative blood vessel diameters in the two cohorts did not differ statistically. Although the postoperative blood velocity and flow volume reduced significantly when compared with the preoperative values, there were no significant inter-group differences. CONCLUSION: TLS contributes to comparable clinical efficacy, safety, hepatic hemodynamics, and liver function as those of OS in treating PH, with a longer OT but lesser intraoperative blood loss.

Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer.

BACKGROUND: Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. AIM: To identify a novel biomarker for early detection of GC. METHODS: Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. RESULTS: There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). CONCLUSION: Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.

Up- and Down-regulated Leukemia-related Protein 16 Affects ERα Expression and Prolactin Secretion by GH3 Cells.

Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16) is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor α (ERα) in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old) were randomly divided into five groups of 10 rats each. After 120 days of treatment, the rats were sacrificed, and the expression of LRP16 and ERα were examined by Western blot and immunohistochemistry to explore the changes in ERα, LRP16, and prolactin. After siRNA transfection of the respective genes, the GH3 cells were cultured, and their secretory function as well as the expression of ERα mRNA and prolactin were analyzed by enzyme-linked immunosorbent assay and real-time-polymerase chain reaction analysis. The results show that secretion of prolactin by GH3 cells can be affected by up and downregulating LRP16 expression, which may provide a novel medical therapy in clinical trials.

The endophytic fungi of Salvia miltiorrhiza Bge.f. alba are a potential source of natural antioxidants.

BACKGROUND: Salvia miltiorrhiza Bge. f. alba is a traditional Chinese herbal drug with special pharmacological effect on thromboangiitis obliterans. However, the nature source of S.miltiorrhiza Bge.f.alba is now in short supply because of the over-collection of the wild plant. To better utilize this resource, the diversity and antioxidant activity of endophytic fungi isolated from S. miltiorrhiza Bge. f. alba were investigated. RESULTS: A total of 14 endophytic fungi were isolated from different parts of S. miltiorrhiza Bge.f.alba. Based on morphological and molecular identification, the endophytic fungi isolated were classified into four genera (Alternaria sp., Fusarium sp., Schizophyllum sp. and Trametes sp.). These fungal extracts were prepared using ethanol and evaluated for their phytochemical compounds and antioxidant activity. Alternaria alternata SaF-2 and Fusarium proliferatum SaR-2 are of particular interest because they yielded all of nine phytochemicals including saponins, phenol, flavonoids, cardiac glycosides, steroids, tannins, alkaloids, anthroquinone and terpenoids. F. proliferatum SaR-2 and A. alternata SaF-2 also exhibited stronger antioxidant activities by FRAP and DPPH method, having the higher levels of phenol and flavonoid than those of plant root. The total amount of phenol and flavonoid quantified were of 21.75, 20.53 gallic acid equivalent per gram and 8.27 and 7.36 µg/mg of quercetin equivalent respectively. These two endophytic fungi (SaR-2 and SaF-2) were found to have comparable scavenging abilities on both FRAP (1682.21 and 1659.05 µmol/mg, respectively) and DPPH-free radicals (90.14% and 83.25%, respectively, at 0.1 mg/mL). This is the first report about isolation of endophytic fungi from S. miltiorrhiza Bge.f.alba and their antioxidant activities. CONCLUSIONS: These results indicate that the endophytic fungi associated with S. miltiorrhiza Bge.f. alba can be a potential source of novel natural antioxidants.

CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition.

PI3K/Akt/mTOR pathway plays an important role in tumor progression and anti-cancer drug resistance. The aim of the present study is to determine the antitumor effect of CCT128930, a novel small molecule inhibitor of Akt, in the HepG2 hepatoma cancer cells. Our results showed that at low concentrations, CCT128930 increased, but not inhibited, the phosphorylation of Akt in HepG2 and A549 cells. CCT128930 inhibited cell proliferation by inducing cell cycle arrest in G1 phase through downregulation of cyclinD1 and Cdc25A, and upregulation of p21, p27 and p53. A higher dose (20 µM) of CCT128930 triggered cell apoptosis with activation of caspase-3, caspase-9, and PARP. Treatment with CCT128930 increased phosphorylation of ERK and JNK in HepG2 cells. CCT128930 activated DNA damage response of HepG2 cell characterized by phosphorylation of H2AX, ATM (ataxia-telangiectasia mutated), Chk1 and Chk2. Upon exposure to CCT128930 at a higher concentration, HepG2 cells exhibited autophagy was accompanied by an increase the levels of LC3-II and Beclin-1. Blocking autophagy using chloroquine magnified CCT128930-induced apoptotic cell death and the phosphorylation of H2AX. The results in this study have advanced our current understandings of the anti-cancer mechanisms of CCT128930 in cancer cells.