Portal Venous and Hepatic Arterial Coefficients Predict Post-Hepatectomy Overall and Recurrence-Free Survival in Patients with Hepatocellular Carcinoma: A Retrospective Study.

Background: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534-2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290-1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149-2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380-2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005-2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236-2.263), higher BCLC stage (HR 1.516, 95% CI 1.300-1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198-2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060-1.997). Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.

Brucine suppresses proliferation and promotes apoptosis of human cholangiacarcinoma cells via the inhibition of COX2 expression.

Aims The aim of this study was to investigate the anti-tumor efficacy of brucine on intrahepatic cholangiocarcinoma (ICC). Methods ICC QBC939 cells were treated with brucine, cell viability, cell cycle and apoptosis were analyzed using CCK-8 and flow cytometry. The expression of COX-2 and apoptosis related proteins Casp3, Bax and Bcl-2 were detected by Western blot analysis. QBC939 cells were subcutaneously transplanted into nude mice and the mice were injected with brucine intraperitoneally. The expression of Ki67, COX-2 and apoptosis related proteins were detected by immunohistochemical staining and Western blot analysis. Results Brucine significantly inhibited the proliferation and cell cycle progression while promoted the apoptosis of QBC939 cells. The expression of the apoptotic proteins Casp3 and Bax was upregulated, while the expression of Bcl-2 and COX-2 was downregulated in QBC939 cells with brucine treatment. Moreover, the overexpression of COX-2 could antagonize the effects of brucine on QBC939 cells. In vivo, brucine inhibited subcutaneous tumor formation in nude mice, and the expression of Ki67, COX-2 and Bcl-2 decreased while the expression of Casp3 and Bax increased in tumor tissues from nude mice with brucine treatment. Conclusions Brucine can significantly inhibit the progression of cholangiocarcinoma in vitro and in vivo, and the mechanism may be related to the inhibition of COX-2 expression.

First-Principles Study on Mechanical and Optical Behavior of Plutonium Oxide under Typical Structural Phases and Vacancy Defects.

The chemical corrosion aging of plutonium is a very important topic. It is easy to be corroded and produces oxidation products of various valence states because of its 5f electron orbit between local and non-local. On the one hand, the phase diagram of plutonium and oxygen is complex, so there is still not enough research on typical structural phases. On the other hand, most of the studies on plutonium oxide focus on PuO2 and Pu2O3 with stoichiometric ratio, while the understanding of non-stoichiometric ratio, especially for Pu2O3-x, is not deep enough. Based on this, using the DFT + U theoretical scheme of density functional theory, we have systematically studied the structural stability, lattice parameters, electronic structure, mechanical and optical properties of six typical high temperature phases of ß-Pu2O3, α-Pu2O3,γ-Pu2O3, PuO, α-PuO2,γ-PuO2. Further, the mechanical properties and optical behavior of Pu2O3-x under different oxygen vacancy concentrations are analyzed and discussed in detail. The result shows that the elasticity modulus of single crystal in mechanical properties is directly related to the oxygen/plutonium ratio and crystal system. As the number of oxygen vacancies increases, the mechanical constants continue to increase. In terms of optical properties, PuO has the best optical properties, and the light absorption rate decreases with the increase of oxygen vacancy concentration.

Expression and clinical significance of EGR-1 and PTEN in the pituitary tumors of elderly patients.

The aim of the study was to investigate the expression and clinical significance of early growth response protein 1 (EGR-1) and phosphatase and tensin homolog (PTEN) in the pituitary tumors of elderly patients. From January 2014 to December 2015, we collected 25 patient cases with non-invasive pituitary tumors, 10 cases with invasive pituitary tumors and 35 cases with healthy pituitary tissues (the healthy control group). Immunohistochemical staining was used to detect the expression of EGR-1 and PTEN, and analyze specific differences. The expression of EGR-1 and PTEN in patients with invasive and non-invasive pituitary tumors increased significantly, when compared with the healthy control group, and the difference was statistically significant (p<0.05). In patients with invasive tumors, EGR-1 levels were higher than levels in patients with non-invasive tumors. The difference was statistically significant (p<0.05). PTEN levels in patients with invasive tumors were significantly lower than levels in patients with non-invasive tumors. The difference was statistically significant (p<0.05). In conclusion, EGR-1 and PTEN levels in patients with pituitary tumors were significantly higher. In addition, EGR-1 levels were higher in patients with invasive pituitary tumors, while PTEN levels were lower. The combination of increases in both levels highlights an important role in the evaluation and prognosis of elderly patients with pituitary tumors.

Serum Cripto-1 is a novel biomarker for non-small cell lung cancer diagnosis and prognosis.

INTRODUCTION: Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined. OBJECTIVES: The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC. METHODS: Serum specimens from 592 NSCLC patients, 180 benign lung disease patients and 240 healthy controls were collected. The concentrations of CR-1 were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: Patients with NSCLC had higher serum CR-1 levels than the controls (P < 0.01) and patients with benign lung diseases (P < 0.01). When a cutoff point of 1.8 ng/mL was selected (diagnostic specificity 95%), the diagnostic sensitivity for NSCLC is 56.8%. About 37.5% of carcinoembryonic antigen (CEA)-negative lung cancer patients were CR-1 positive at 95% specificity. In patients with stage I/II lung cancer, use of these two markers in combination results in almost 21% increase in sensitivity, at 95% specificity, compared with CEA alone. Uni-variate analysis revealed that NSCLC patients with positive CR-1 had a shorter overall survival (OS) and progression-free survival (PFS) than those with negative CR-1 [hazard ratio (HR) of 2.93, P = 0.005; HR of 2.12, P = 0.005]. Cox multi-variate analysis indicated that CR-1 was an independent prognostic indicator of PFS and OS (HR of 1.91, P = 0.006; HR of 1.82, P = 0.007). Kaplan-Meier survival curves further confirmed that patients with negative CR-1 had longer PFS and OS (P = 0.026 and P = 0.011, respectively). CONCLUSIONS: In conclusion, measurement of serum CR-1 is a useful diagnostic and prognostic marker for NSCLC patients.

Diagnostic and prognostic value of serum periostin in patients with non-small cell lung cancer.

The periostin protein is expressed in a variety of human malignancies. The aim of this study was to explore the diagnostic and prognostic value of serum periostin levels in patients with non-small cell lung cancer (NSCLC). We measured serum periostin levels by ELISA in 296 NSCLC patients, 120 benign lung diseases (BLD) patients and 160 healthy controls. The levels of serum periostin in NSCLC patients were significantly elevated compared with those in healthy controls (P < 0.001) and BLD patients (P < 0.001). Using a cutoff value of 30.87 ng/ml, the sensitivity and specificity of periostin in differentiating between NSCLC patients and BLD patients, and between NSCLC patients and healthy controls was, 48.6 and 91.7%, and 51.4 and 97.5%, respectively. Kaplan-Meier log rank analysis revealed that the higher serum periostin levels group had a poorer progression-free survival (PFS) and overall survival (OS) compared with lower periostin group (P = 0.024, P = 0.015, respectively). Further univariate and multivariate Cox regression analysis showed that serum periostin was an independent risk factor of prognosis of NSCLC patients. In conclusion, our study suggests that serum periostin could be considered as a diagnostic and prognostic marker for NSCLC patients.

IFN-γ secretion in gut of Ob/Ob mice after vertical sleeve gastrectomy and its function in weight loss mechanism.

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.

Elevated expression of Cripto-1 correlates with poor prognosis in non-small cell lung cancer.

Human Cripto-1 (CR-1) plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of carcinomas, yet little is known about CR-1 in non-small cell lung cancer (NSCLC). The aims of this study were to detect CR-1 expression in NSCLC and to analyze its association with prognosis of NSCLC patients. The expression of CR-1 messenger RNA (mRNA) and protein in 35 cases of NSCLC and corresponding noncancerous tissue samples was examined by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Immunohistochemistry was performed to detect the expression of CR-1 in 128 NSCLC tissues. The expression levels of CR-1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding noncancerous tissues (P < 0.001). A high level of CR-1 expression was correlated with poor tumor differentiation (P = 0.002), tumor-node-metastasis (TNM) stage (P = 0.004), and lymph node metastasis (P = 0.001). The results of the Kaplan-Meier analysis indicated that a high expression level of CR-1 resulted in a significantly poor prognosis of NSCLC patients. Multivariate Cox regression analysis revealed that CR-1 expression level was an independent prognostic parameter for the overall survival rate of NSCLC patients. Our data suggest that the high expression of CR-1 may play an important role in the progression of NSCLC, and CR-1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

Baseline and decline of serum ADAM28 during chemotherapy of advanced non-small cell lung cancer: a probable predictive and prognostic factor.

ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small cell lung cancer (NSCLC) with correlation to cancer proliferation, tumor size and lymph node metastasis. In the present study, we investigated the predictive and prognostic value of ADAM28 during chemotherapy in patients with advanced NSCLC. 122 advanced NSCLC cases, 37 patients with benign lung disease and 40 healthy controls were enrolled in the study. The serum levels of ADAM28 were measured by enzymelinked immunosorbent assays. Data were correlated with diagnosis, radiologic objective response and survival. Serum levels of ADAM28 in advanced NSCLC group were significantly elevated compared to benign lung disease group (P<0.001) and healthy controls (P<0.001). And the expression of ADAM28 had relationship to the tumor size and lymph metastasis in NSCLC patients. When the cut-off value of ADAM28 was 225.54 pg/ml, the area under the ROC curve was 0.843 (95% confidence interval [CI]: 0.784-0.902); the sensitivity (SEN) and specificity (SPE) were both the best, with a SEN of 76% and a SPE of 83%. The patients who had ADAM28-response and no ADAM28-response had significantly difference in objective response to treatment (P<0.001). The median Progression-free survival from response assessment was 5 months. In the multivariate analysis, performance status (hazard ratio [HR], 1.68; 95% CI: 1.06-2.67), the level of serum ADAM28 (HR, 1.01; 95% CI: 1.01-1.02), and ADAM28-responses (HR, 047; 95% CI, 0.26-0.83), were significant correlated with prognosis. The levels of ADAM28 and ADAM28-responses appeared to be reliable surrogate markers to predict tumor response and survival in patients with advanced NSCLC.