Identification of neutrophil-related genes and development of a prognostic model for cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored. METHODS: A comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA-CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single-sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). RESULTS: The study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil-related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD-L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration. CONCLUSIONS: This study elucidates a neutrophil-related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment.

Relevant detection indicator of prethrombotic state in patients with primary hypertension.

BACKGROUND: Hypertension is a common chronic disease that affects many people worldwide. Only a few reports related to the exploration of relevant indicators of the prethrombotic state in patients with primary hypertension (PH) in clinical settings were available. AIM: To detect prethrombotic state-related indicators in patients with PH and analyze their differences in different patient populations to provide a laboratory basis for the clinical prevention and control of hypertensive thrombotic diseases. METHODS: The general data of patients with PH who attended the Department of Cardiovascular Medicine, The First Affiliated Hospital of Jiangxi Medical College, from January 2022 to December 2022 were collected retrospectively. The patients were divided into three groups of 40 patients each according to the Grade of PH: Grade 1, Grade 2, and Grade 3 hypertension experimental group. The baseline data of 40 volunteers, who underwent physical examination in our hospital but were not diagnosed with PH during the same period, were included in the control group. The relevant indicators of prethrombotic state of the participants were compared, and mainly included inflammation-related indicators, hemorheology-related indicators, and coagulation function related indicators. The relationship between the aforementioned indicators and the progression of PH was analyzed. RESULTS: No significant differences were observed in age, sex, diabetes mellitus, smoking history, drinking history, body mass index, New York Heart Association functional classification, or the course of hypertension among the four groups (P > 0.05). The expressions of high-sensitivity C-reactive protein (hs-CRP), thrombomodulin (TM), hematocrit (Hct), erythrocyte sedimentation rate (ESR), P-selectin on platelet surface (CD62P), and fibrinogen (FIB) in the control group were < Grade 1 hypertension group < Grade 2 hypertension group < Grade 3 hypertension group, and the expressions of platelet (PLT), activated partial thromboplastin time (APTT), prothrombin (PT), and plasma thrombin time (TT) in the control group was > Grade 1 hypertension group > Grade 2 hypertension group > Grade 3 hypertension group, and the difference was statistically significant (P < 0.05). The results of the multivariate logistic regression model showed that the expression of hs-CRP, TM, Hct, ESR, CD62P, PLT, APTT, PT, TT, and FIB in the included participants was related to the progression of PH. Among these, high expression of hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT, and low expression of PLT and FIB were risk factors for PH (OR > 1, P < 0.05). The results of the receiver operating characteristic curve analysis showed that the area under the curve of hs-CRP, TM, ESR, CD62P, APTT, PT, TT, and FIB for the prediction of PH were > 0.80, and the prediction value was ideal. Linear correlation analysis with bivariate Spearman showed that hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT were positively correlated with each other (r > 0, P < 0.05); PLT and FIB were negatively correlated with hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT (r < 0, P < 0.05); and PLT and FIB were positively correlated (r > 0, P < 0.05). Linear correlation analysis using bivariate Spearman showed that hs-CRP, TM, Hct, ESR, CD62P, and FIB were positively correlated with each other (r > 0, P < 0.05), whereas PLT, APTT, PT, and TT were negatively correlated with hs-CRP, TM, Hct, ESR, CD62P, and FIB (r < 0, P < 0.05). There was a positive correlation between PLT, APTT, PT, and TT (r > 0, P < 0.05). CONCLUSION: The relevant indicators of the prethrombotic state in patients with PH, such as hs-CRP, TM, Hct, ESR, CD62P, PLT, APTT, PT, TT, and FIB, showed differences. High expression of hs-CRP, TM, Hct, ESR, CD62P, and FIB, and low expression of PLT, APTT, PT, and TT are the keys to the occurrence, progression, and thrombotic state of PH. Based on the above serum indicators' expression in patients, targeted interventions can be administered to patients with abnormal expression levels to control the progression of their disease and reduce the risk of developing a prethrombotic state.

Treatment with sorafenib plus camrelizumab after splenectomy for primary splenic angiosarcoma with liver metastasis: A case report and literature review.

BACKGROUND: Primary splenic angiosarcoma (PSA) is an extremely rare and aggressive mesenchymal malignancy with high metastatic potential and a poor prognosis. There are no established treatment guidelines for PSA, even for adjuvant therapy. This rare case may provide a reliable therapeutic regime for a better prognosis. CASE SUMMARY: A 49-year-old female who complained of right-upper quadrant abdominal pain was diagnosed as having PSA with splenic rupture and liver metastasis. After splenectomy and liver tumor resection, she received sorafenib and camrelizumab therapy. After 15 mo of follow-up, she is in good condition, without recurrence or any identified metastasis. CONCLUSION: Immunotherapy combined with targeted therapy could be a potential option for the adjuvant therapy of PSA.

AOC1 Contributes to Tumor Progression by Promoting the AKT and EMT Pathways in Gastric Cancer.

BACKGROUND: AOC1 is a copper-containing amine oxidase that is responsible for catalyzing the deamination of polyamines, which produces reactive oxygen species. Previous studies have demonstrated that polyamines are involved in the regulation of proliferation, migration, and apoptosis of cells. However, very little is known about the functions and regulatory mechanisms of AOC1 in tumors. METHODS: Based on GEPIA data, we found that AOC1 was significantly upregulated in human gastric cancer tissues. We knocked down AOC1 in human AGS and MKN45 cells using siRNA transfection, then utilized qRT-PCR assay and Western blot to verify the effectiveness of AOC1 knockdown in gastric cancer cells. RESULTS: Function analysis demonstrated that knockdown of AOC1 inhibited the proliferation, invasion, and migration of human gastric cancer cells. Flow cytometry detection suggested that AOC1 knockdown induced apoptosis in human gastric cancer cells. Mechanism investigation suggested that AOC1 knockdown increased the ratio of Bax/Bcl2 and induced activation of the caspase cascade. Furthermore, the AKT signaling pathway was inactivated when AOC1 was silenced, including downregulated phosphorylation level of AKT and expression of downstream effectors, Cyclin D1, and p70S6K. Finally, we found that knockdown of AOC1 inhibited the epithelial-mesenchymal transition (EMT) in human gastric cancer by increasing the expression of epithelial markers E-cadherin, as well as decreasing mesenchymal marker N-cadherin, SNAIL and Slug. CONCLUSION: Our study suggests that AOC1 functions as an oncogene in human gastric cancer by activating the AKT signaling pathway and EMT process and maybe a target of 6-mercaptopurine, which provides new insight in the clinical use of AOC1 in gastric cancer therapy.

Clinical significance and prognostic value of urinary nucleosides in breast cancer patients.

OBJECTIVE: Thirteen urinary nucleosides, primarily degradation products of tRNA, were evaluated as potential tumor markers for breast cancer patients. DESIGN AND METHODS: The micellar electrokinetic chromatography (MEKC) method has been used to analyze the urinary nucleosides in 41 healthy controls, 20 patients with benign breast tumors, and 26 breast cancer patients. RESULTS: Urinary nucleoside concentrations of breast cancer patients were found to increase significantly compared to those of patients with benign breast tumors and healthy controls. By using 13 nucleoside concentrations as data vectors for principal component analysis (PCA), 73% (19/26) of breast cancer patients were correctly identified from healthy controls, while only 20% (4/20) of patients with benign breast tumors were indistinguishable from breast cancer patients. The mean level of all forms of urinary nucleosides in patients with metastatic breast cancer was higher than that in patients with primary breast cancer. The levels of modified nucleosides tended to decrease and return to normal after surgery. CONCLUSION: The results indicate that urinary nucleosides may be useful as tumor markers for breast cancer.

[Determination of curcumin in urine by capillary electrophoresis].

The major component of the plant curcuma longa (a widely cultivated tropical plant in Asia and Central America) is curcumin. Curcumin has been reported to have very strong anti-inflammatory, anti-carcinogenic, anti-oxidant, antiallergic, anti-bacterial, and anti-tumor activities. Little is known about the absorption, distribution, and metabolism of curcumin in human beings. The first step in in vivo physiological and pharmacokinetic studies is to develop a method to measure curcumin in body fluid. A rapid capillary electrophoretic (CE) method with diode array detection was established for the determination of curcumin in human urine. It could be rapidly determined within 2.5 min. The optimized experimental conditions were as follows: 15 mmol/L Na2B4O7 as buffer, applied voltage 20 kV, temperature 25 degrees C and detection wavelength 262 nm. The method has been validated and shows good performance with respect to selectivity, reproducibility and limit of detection. Curcumin had good linearity in the range of 10 - 300 mg/L, and the recoveries of curcumin added in urine were more than 96.3% with relative standard deviations (RSDs) less than 2.3%. The method is sensitive, fast and accurate and can be used to determine curcumin in urine.

Study of urinary nucleosides as biological marker in cancer patients analyzed by micellar electrokinetic capillary chromatography.

Thirteen normal and modified nucleosides, primarily degradation products of transfer ribonucleic acid (tRNA), were evaluated as potential tumor markers for cancer patients. Their urinary concentrations were determined by means of micellar electrokinetic capillary chromatography (MEKC) in the urine from 54 healthy adults and 70 cancer patients, then quantitatively expressed as a function of creatinine excretion. It was found that urinary nucleosides for cancer patients were on the average significantly higher than those for healthy controls, however, no significant differences were found between male and female or between different ages. Based on 13 urinary nucleoside concentrations, principal component analysis (PCA) could be used to classify 72% of cancer patients from the healthy controls. The present study shows that the precise measurement of urinary nucleosides by MEKC in combining with PCA technique may provide a clinically useful approach for diagnosis of cancer.