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The distribution of fractures in the underground rock mass is complex, so it is of great significance to study the parameter characteristics of fracture seepage for geothermal exploitation, land subsidence, and other fields. Based on the Weierstrass-Mandelbrot function, several X-shaped fracture models with different roughness are established, and the fracture seepage law under different roughness and inlet pressure is studied. At the same time, the center (cross-region) of the X-shaped fracture is selected as the research object, and the seepage difference characteristics of the cross-region under the two inlet modes of adjacent flow and convective flow are compared and analyzed. The results show that the outlet velocity of fracture fluid is inversely proportional to the fractal dimension and is directly proportional to the inlet pressure.

Background: Forkhead box C1 (FOXC1) is an important cancer-associated gene in tumor. PPAR-γ and C/EBPα are both transcriptional regulators involved in tumor development. Objective: We aimed to clarify the function of PPAR-γ, C/EBPα in hepatocellular carcinoma (HCC) and the relationship of PPAR-γ, C/EBPα and FOXC1 in HCC. Methods: Western blotting, immunofluorescent staining, and immunohistochemistry were used to evaluate protein expression. qRT-PCR was used to assess mRNA expression. Co-IP was performed to detect the protein interaction. And ChIP and fluorescent reporter detection were used to determine the binding between protein and FOXC1 promoter. Results: C/EBPα could bind to FOXC1 promoter and PPAR-γ could strengthen C/EBPα’s function. Expressions of C/EBPα and PPAR-γ were both negatively related to FOXC1 in human HCC tissue. Confocal displayed that C/EBPα was co-located with FOXC1 in HepG2 cells. C/EBPα could bind to FOXC1 promoter by ChIP. Luciferase activity detection exhibited that C/EBPα could inhibit FOXC1 promoter activity, especially FOXC1 promoter from -600 to -300 was the critical binding site. Only PPAR-γ could not influence luciferase activity but strengthen inhibited effect of C/EBPα. Further, the Co-IP displayed that PPAR-γ could bind to C/EBPα. When C/EBPα and PPAR-γ were both high expressed, cell proliferation, migration, invasion, and colony information were inhibited enormously. C/EBPα plasmid combined with or without PPAR-γ agonist MDG548 treatment exhibited a strong tumor inhibition and FOXC1 suppression in mice. Conclusion: Our data establish C/EBPα targeting FOXC1 as a potential determinant in the HCC, which supplies a new pathway to treat HCC. However, PPAR-γ has no effect on FOXC1 expression.

The pharmacokinetic (PK) and potential effects of Emodin on liver cancer were systematically evaluated in this study. Both the intragastric administration (i.g.) and hypodermic injection (i.h.) of Emodin exhibited a strong absorption (absorption rate human> beagle dog. These PK data provided the basis for the subsequent animal experiments. In liver cancer patient tissues, the expression of vascular endothelial growth factor (VEGF)-induced signaling pathways, including phosphorylated VEGF receptor 2 (VEGFR2), AKT, and ERK1/2,were simultaneously elevated, but miR-34a expression was reduced and negatively correlated with SMAD2 and SMAD4. Emodin inhibited the expression of SMAD2/4 in HepG2 cells by inducing the miR-34a level. Subsequently, BALB/c nude mice received a daily subcutaneous injection of HepG2 cells with or without Emodin treatment (1 mg/kg or 10 mg/kg), and Emodin inhibited tumorigenesis and reduced the mortality rate in a dose-dependent manner. In vivo experiments showed that cell proliferation, migration, and invasion were promoted by VEGF or miR-34a signal treatment but were inhibited when combined with Emodin treatment. All these results demonstrated that Emodin inhibited tumorigenesis in liver cancer by simultaneously inhibiting the VEGFR2-AKT-ERK1/2signaling pathway and promoting a miR-34a-mediated signaling pathway.

C–S–H-PCE nanocomposites (CPNs) serving as nucleation sites are a promising material to accelerate the cement hydration and gain high early strength for cementitious materials. This study aimed to investigate the effects of CPNs on the properties and hydration of cement mortar under different water-to-cement (w/c) ratios. CPNs were prepared via the co-precipitation method in MAPEG-PCE solution and characterized by means of XRD, FT-IR, DLS, TEM , TGA, and TOC . The mechanism and effect of CPNs on the early hydration of cement mortar with w/c ratios of 0.50, 0.40, and 0.35 were assessed in terms of mechanical properties, isothermal calorimetry, setting time XRD, TGA, SEM, and MIP. The results showed that CPNs significantly promoted the early strength development of mortar and a higher enhancement ratio was brought at a lower w/c ratio. Calorimetry and setting results also showed a greater hydration acceleration of samples dosed CPNs with lower w/c ratio. From the analysis of XRD and TGA, the content of CH and C–S–H in the samples dosed CPNs increased with the decrease of w/c ratio in 6 h, while exhibited an opposite trend in 12 h and 3 d. MIP and SEM results showed that CPNs led to a refinement of pore structure and dense morphology, especially at a low w/c ratio. Moreover, the underlying acceleration mechanism of cement hydration versus w/c ratio was that the seeding ability was enhanced for the low distance between cement and CPNs at a low w/c ratio. According to this research, the use of CPNs may be more practical in high-strength concrete.

Intrahepatic cholangiocarcinoma (IHCC) is an aggressive cancer with a poor survival rate and is the second most common type of primary cancer of the hepatobiliary system. At present, the molecular mechanisms of IHCC initiation and progression remain unclear. Recent evidence has indicated that long non‑coding RNAs (lncRNAs) serve a crucial role in cancer development; however, the functional role of lncRNAs in IHCC has not been investigated in detail. In the present study, a marked overexpression of lncRNA colon cancer‑associated transcript 2 (CCAT2) was observed in IHCC cell lines and clinical specimens. Statistical analysis of IHCC clinicopathological characteristics and CCAT2 expression data revealed that high CCAT2 expression levels correlated with microvascular invasion, differentiation grade, tumor (T), lymph node (N), metastasis (M) and overall TNM stages of IHCC (P

It has been reported that dendritic cells (DCs) play a crucial role in the host’s immune defense against tumors, and there is an inverse correlation between the density of DCs and the expression of vascular endothelial growth factor (VEGF). However, the relationship between the expression of VEGF-C and DC infiltration remained unclear. In the present study, we investigated whether the expression of VEGF-C correlated with the number of DCs in vivo. We immunohistochemically analyzed gastric carcinoma tissue in this study. The survival curves show that the prognosis for patients with a low density of DCs was significantly poorer than that for patients with high DC density (p < 0.01). Further, the survival curves according to the VEGF-C status showed that the survival rate in patients with low VEGF-C expression was higher than that in patients with higher expression (p < 0.01). There was a significant negative correlation between the density of DCs and the expression of VEGF-C (r = –0.26, p < 0.05). We suggest that VEGF-C produced by cancer causes DCs to become dysfunctional. This may be one of the ways that cancers evade immunosurveillance.

Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in cancer growth. In this study, we characterized VEGF-C expression in cultured human pancreatic cancer cell lines and determined whether the presence of VEGF-C in human pancreatic cancers is associated with clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all five tested cell lines (Capan-1, MIA-PaCa-2, PANC-1, COLO-357, and T3M4). Immunoblotting with a highly specific anti-VEGF-C antibody revealed the presence of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA revealed an approximately 2.2-fold increase in VEGF-C mRNA transcript in the cancer samples compared with the normal pancreas. Immunohistochemical analysis confirmed the expression of VEGF-C and its receptor flt-4 in the cancer cells within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer tissues revealed the presence of strong VEGF-C immunoreactivity in the cancer cells in 80.4% of the cancer tissues. The presence of VEGF-C in these cells was associated with increased lymphatic vessels invasion and lymph node metastasis, but not with decreased patient survival. These findings indicate that VEGF-C and its receptor are commonly overexpressed in human pancreatic cancers and that this factor may contribute to the lymphangiogenic process and metastasis in this disorder.

Most hepatocellular carcinomas (HCCs) first occur as well-differentiated HCCs, from which poorly differentiated HCC cells develop because of dedifferentiation. In this study, we try to clarify the changes of dedifferentiation and cell proliferative activity and their relationship in small HCCs (less than 3.0 cm in diameter) and try to learn the mechanism of these changes by analysing the expressions and genetic changes of proliferation-related genes p53 and beta-catenin. Of 41 surgically resected small HCCs, 11 were identified to have tumor heterogeneity. DNA from the 11 small HCCs, consisting of 29 intratumoral lesions and 11 noncancerous liver tissues adjacent to HCCs, was extracted from paraffin embedded tissue sections. Exons 5-8 of p53 gene and exon 3 of beta-catenin gene were amplified by polymerase chain reaction and analyzed by direct sequence. The serial sections were also immunostained by anti-Ki-67, p53 and beta-catenin antibody. Immunohistochemistry showed that the p53 overexpression was significantly related to the proliferative activities as evaluated by Ki-67 immunostaining and to the histological differentiation. The expression of beta-catenin was found to be heterogeneously distributed not only in various histological grades of the same tumor but also in areas of the same histological grade. p53 and beta-catenin gene mutations were detected in 1 tumor respectively, both of which were second primary HCCs and also recurred later. The p53 mutation showed the same mutation pattern in heterogeneous subpopulations. beta-catenin mutation was detected only in the less differentiated lesion but not in the well-differentiated lesion of tumor. In conclusion, our findings suggest that there was histological heterogeneity in small but established HCC, which was accompanied by increased proliferative activity and p53 overexpression. The overexpression of beta-catenin may be related to the proliferative activity and dedifferentiation of HCC.

To investigate the expression of RKIP, p65 and pERK in hepatocellular carcinoma (HCC) and theIr correlation with invasion and metastasis of HCC.Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RKIP mRNA. The expression levels of RKIP, p65 and pERK proteins in HCC tumor and peritumoral tissues were determined by immunohistochemistry and Western blot analysis. Statistical analysis was performed to determine the relationship between their expression and clinicopathological parameters.RKIP protein expression level (RKIP/actin) was 0.579 ± 0.380 in HCCs, 1.178 ± 0.659 in peritumoral tissues and 1.115 ± 0.442 in normal liver tissues. The pERK protein level was 1.023 ± 0.478, 0.605 ± 0.367 and 0.461 ± 0.293, p65 protein level was 0.83 ± 0.376, 0.63 ± 0.337 and 0.466 ± 0.345, respectively. Immunohistochemistry analysis showed that the RKIP positive rates in HCCs, peritumoral tissues and normal liver tissues, were 22.2%, 86.0%, and 93.8%, positive rates of p65 were 73.6%, 56.0% and 37.5%, positive rates of pERK were 65.3%, 38.0% and 31.3%, respectively. Statistical analysis revealed that there was a significant difference in RKIP protein expression levels (P0.05), but no significant difference in RKIP mRNA expression levels (P0.05) among HCC tumors, peritumoral tissues and normal liver tissues. The p65-positive and pERK-positive rates were higher in tumor tissues than that in peritumoral tissues and in normal liver tissues (P0.05), but RKIP-positive rates were lower in tumor tissues than that in paritumoral tissues and normal liver tissues (P0.05). RKIP protein expression levels were significantly lower in HCCs with intrahepatic or lymphatic metastasis than that in without. The RKIP positive rates in moderately and well differentiated HCCs were significantly higher than that in poorly differentiated HCCs. There was a relationship between RKIP and pERK expressions (P = 0.04), but RKIP expression was not correlated with p65 expression in HCCs (P = 0.143).Our findings indicate that the down-regulation of RKIP expression may serve as a predictive marker for HCC development, progression and metastasis, which may contribute to the elevated ERK activity. The inhibiting effect of RKIP on invasion and metastasis of liver cancer cells may be due to the down-regulation of pERK expression rather than p65 expression.

Liver metastasis is one of the poor prognostic factors for gastric cancer. Hepatocyte growth factor (HGF) and its receptor, c-Met, have been reported to be related to the proliferation of carcinoma cells. We examined c-Met and HGF expression in stage IV gastric cancers (n = 121) and compared the results in groups with liver metastasis (n = 47, LM group) and without liver metastasis (n = 74, no-LM group). The survival rate for the LM group was significantly poorer than for the no-LM group (p < 0.01). We found a high frequency of c-Met expression in the LM group compared with the no-LM group at protein level detected by immunohistochemistry (p = 0.0005) and at mRNA level detected by semiquantitative reverse transcriptase-polymerase chain reaction (p = 0.0386) in primary gastric tumors. Furthermore, we evaluated HGF expression in both carcinoma cells and stromal cells in gastric cancers. There was no significant difference in the HGF expression between the LM and no-LM groups. The labeling index of proliferating cell nuclear antigen for the carcinomas in the LM group was higher than that in the no-LM group (47.1 ± 24.5 vs. 26.2 ± 24.5%, p < 0.0001). Thus, the high frequency of c-Met overexpression in carcinoma cells may be involved in the mechanism of liver metastasis in gastric cancers. Moreover, the evaluation of c-Met expression might be a useful indicator of liver metastasis in patients with gastric cancer.

AIM: To study the expression of vascular endothelial growth factor A (VEGF - A) and VEGF - C and to determine whether the presence of VEGF - A and VEGF - C was associated with the clinicopathologic characteristics of pancreatic cancer. METHODS: VEGF - A and VEGF - C mRNA transcripts were examined by Northern blot in 6 human pancreatic cancer cell lines and 8 normal pancreatic tissues and 8 pancreatic carcinoma specimens. The expression of VEGF - A and VEGF - C proteins was examined by Western blot in the tested cell lines and by immunohistochemical stain in 50 pancreatic carcinoma samples. RESULTS: VEGF - A and VEGF - C mRNA transcripts were present in all the 6 human pancreatic cancer cell lines. Immunoblotting revealed the presence of VEGF - A and VEGF - C proteins in all the cell lines. Northern blot analysis of total RNA revealed 3.0-fold and 3.6 - fold increase in VEGF - A and VEGF - C mRNA transcript in the cancer samples, respectively. Immunohistochemical analysis confirmed the expression of VEGF - A and VEGF - C in cancer cells within the tumor mass. Immunohistochemical analysis of 50 pancreatic cancer tissue samples revealed the presence of VEGF-A and VEGF - C immunoreactivity in 50% and 80% of the cancer tissue samples, respectively. The presence of VEGF-A in these cells was associated with larger tumor size and enhanced local spread (χ2 = 6.690, P = 0.035