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To explore the diagnostic value of American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADS) for hepatocellular carcinoma (HCC) in patients with cirrhosis and chronic hepatitis B.A total of 205 patients at high risk of HCC with solitary hepatic nodule were enrolled and retrospectively analyzed. All patients were over 18 years old and had a single lesion with a diameter 50 mm. Lesions were categorized according to size and contrast enhancement patterns in the arterial, portal venous and late phases. Diagnostic efficacy of CEUS LI-RADS for HCC, and the rate of non-HCC malignancies in the LR-M class were compared between patients with cirrhosis and chronic hepatitis B.Of all 205 nodules (median nodule size was 34 mm), 142 (69.3%) were HCC. Of the 127 (61.9%) LR-5 category nodules, 95.8% (92/96) nodules were corresponded to HCC in cirrhosis, while 61.3% (19/31) nodules were corresponded to HCC in chronic hepatitis B (P = 0.000). Positive predictive value (PPV) of LR-5 category for HCC was 95.8% in cirrhosis and 61.3% in chronic hepatitis B (P = 0.000). More category of LR-4 nodules were proved to be HCC in patients with cirrhosis than chronic hepatitis B (80.0% vs 8.3%, P = 0.000). Of 41 LR-M category nodules, more non-HCC malignancies were found in chronic hepatitis B (76.0%) than that in cirrhosis (25.0%, P = 0.001).The LR-5 category is highly specific for the diagnosis of HCC in patients with cirrhosis. However, LR-5 category nodules require further CT or MRI examination or histological confirmation in patients with chronic hepatitis B for its unsatisfactory PPV for HCC.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with poor progrnosis and a high recurrence rate after surgery. To this end, we examined the role of Nanog that is highly expressed in this tumor. NANOG is a transcription factor involved in the pluripotency of embryonic stem cells (ESCs) and the induction of malignancy in cancer stem-like cells (CSCs). Bioinformatic analysis revealed that NANOG may be associated with the development of stem-like traits in GBM. Forced expression of NANOG markedly increased the expression of cancer stem cell markers and promoted the sphere formation and migration of GBM cells. Nanog enhanced the expression of SHH which is required for the maintenance of the positive feedback loop of Hedgehog signaling pathway. Treatment of GBM cells with SANT-1 and GANT61 significantly reduced the tumor progression. These data support a view that reduction of Nanog might have therapeutic benefits in GBM.

To evaluate the correlations between the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and clinicopathologic findings and prognosis, a retrospective study was performed on 197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical resection. The contrast medium we employed in CEUS was SonoVue, which contains microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid shell. This study was approved by the institutional review board with informed consent waived. Patients were classified into an arterial rim-like enhancement group or an arterial non-rim-like enhancement group, and arterial enhancement patterns were correlated with clinicopathologic factors. Overall survival (OS) times were calculated using the Kaplan–Meier method, and differences between groups were compared with the log-rank test. Univariate and multivariate Cox regression models for OS were used to evaluate the independent prognostic factors. The mean and range of ICC tumor size of the arterial rim-like group (59.41 ± 22.09 mm, 20–100 mm) were similar to those of the arterial non-rim-like group (59.82 ± 30.35 mm, 14–162 mm, p = 0.914). Arterial enhancement patterns were correlated with chronic viral hepatitis or cirrhosis, vascular invasion, lymph node metastasis and single/multiple tumors. A total of 78 patients (39.6%) exhibited arterial rim-like enhancement, and the other 119 patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node metastasis (p = 0.000) and number of tumors (p = 0.001) were independent prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC on CEUS is an independent prognostic factor for better OS and may offer new information for predicting the prognosis of ICC patients before surgical resection.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

We established a fire simulation experiment in the harvested site of Larix olgensis plantation and recorded the temperature of each test point at 500, 1000 and 1500 s during the fire by thermocouple temperature measurement. The data were displayed in the form of images to show soil temperature field at each layer during the fire. The results showed that when the wind speed was less than or equal to 2 m·s建立长白落叶松人工林采伐迹地燃烧床试验模型,进行火灾模拟试验,利用热电偶测温系统得出火灾过程中500、1000、1500 s时各层土壤测试点的温度数据,将数据以图像的形式展现,得出火灾过程中各层土壤温度场的变化情况.结果表明: 当风速≤2 m·s

Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver neoplasm, and its clinical characteristics and imaging features are not well understood. The aim of this study was to analyze the clinical profiles and imaging features of PHNETs on contrast-enhanced ultrasound (CEUS) and computed tomography (CT) METHODS: Patients with PHNET between January 2008 and December 2015 were retrospectively identified, and their demographics, laboratory data, and imaging characteristics on CEUS and CT analyzed.Ten consecutive patients with PHNETs were included (including one G1, seven G2, and two G3 of tumor grades).The median age of patient was 45 years (range: 27-72 years), and 60.0% of patients were male. The most common symptom was abdominal pain (60.0%), and cirrhosis was found in 40.0% of patients. Tumors were confined within the liver in 60.0% of patients, while the remaining patients had extra-hepatic metastasis. The tumors revealed hyperechoic in 60% of patients and mixed echoic in 30% of patients on conventional US, displaying intense arterial enhancement followed by washout in the portal and/or the late phases in 80.0% of patients on CEUS and 60% at CT.Although PHNET is a very rare liver tumor, it should be considered as a possible differential diagnosis in the management of hepatic tumors. Most PHNETs were hyperechoic or mixed echoic on conventional US, showing similar enhancement patterns to that of hepatocellular carcinoma on CEUS.

Potassium has a deactivation effect on Cu-SSZ-13 catalyst for selective catalytic reduction of NO with NH3 (NH3-SCR). It was demonstrated that the modification of Cu-SSZ-13 catalysts by Ce could improve its K resistance. The characterization of NH3-TPD and H2-TPR suggested that the introduction of Ce on Cu-SSZ-13 could improve its surface acidity and redox ability. Moreover, the content of Cu2+ and chemisorbed oxygen were markedly restored under the situation that Ce and K elements were coexistent on catalyst surface. The synergetic effect between Ce and Cu might be the major reason for the great K resistance and the excellent SCR performance.

A novel ball-flowerlike catalyst (CoMnOx-BF) was developed by hydrothermal method for the selective catalytic reduction (SCR) of NOx by NH3. Besides, a counterpart sample (CoMnOx) was prepared by coprecipitation way for comparison. The activity test results demonstrated that CoMnOx-BF catalyst exhibited admirable SCR performance and N2 selectivity in a broad temperature range of 150–350 °C, along with an excellent resistance to SO2 and high durability. Based on characterization experiments, it could be found that the superior surface area resulted from suppressed crystallization, the enrichment of surface labile oxygen and Mn4+, the stronger surface acidity and redox ability were all beneficial to the NH3-SCR performance of CoMnOx-BF catalyst. Additionally, the enhanced NO oxidation and more activated ad-reactants on catalyst surface could also conduce to the outstanding SCR activity of CoMnOx-BF at low temperature.

Microenvironmental regulation of cancer stem cells (CSCs) strongly influences the onset and spread of cancer. The way in which glioma cells interact with their microenvironment and acquire the phenotypes of CSCs remains elusive. We investigated how communication between vascular endothelial cells and glioma cells promoted the properties of glioma stem cells (GSCs). We observed that CD133+ GSCs were located closely to Shh+ endothelial cells in specimens of human glioblastoma multiforme (GBM). In both in vitro and in vivo studies, we found that endothelial cells promoted the appearance of CSC-like glioma cells, as demonstrated by increases in tumourigenicity and expression of stemness genes such as Sox2, Olig2, Bmi1 and CD133 in glioma cells that were co-cultured with endothelial cells. Knockdown of Smo in glioma cells led to a significant reduction of their CSC-like phenotype formation in vitro and in vivo. Endothelial cells with Shh knockdown failed to promote Hedgehog (HH) pathway activation and CSC-like phenotype formation in co-cultured glioma cells. By examination of glioma tissue specimens from 65 patients, we found that the survival of glioma patients was closely correlated with the expression of both Shh by endothelial cells and Gli1 by perivascular glioma cells. Taken together, our study demonstrates that endothelial cells in the tumour microenvironment provide Shh to activate the HH signalling pathway in glioma cells, thereby promoting GSC properties and glioma propagation. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

Osteosarcoma is the most common type of bone cancer, and the second leading cause of cancer-related death in children and young adults. Osteosarcoma stem cells are essential for osteosarcoma initiation, metastasis, chemoresistance and recurrence. In the present study, we report that: 1) higher TSSC3 expression indicates a better prognosis for osteosarcoma patients, and; 2) overexpression of TSSC3 significantly decreases sphere-forming capacity, tumor initiation, stemness-related surface markers and Nanog expression in osteosarcoma cells. We also discovered that higher Nanog expression correlates to a worse prognosis for osteosarcoma patients, and overexpression of Nanog increases the stem-related phenotype in osteosarcoma cells. Knockdown of Nanog suppresses these phenotypes. Inhibition of Nanog expression and self-renewal of osteosarcoma cells by TSSC3 overexpression appears to be mediated through inactivation of the Src/Akt pathway. In the clinical setting, expression of TSSC3, p-Src and Nanog is associated with recurrence, metastasis and surgical intervention. Lower TSSC3 expression, higher Nanog expression or higher p-Src expression indicate a poor prognosis for osteosarcoma patients. Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.

By utilizing the theory of green design and green manufacture，the paper discusses advanced design concept and modern manufacturing concept, and probes into the model of clean manufacture and sustained development thinking in machine tool and hydraulics system.

Objectives We previously found niacin receptor GPR109A was expressed in murine islet beta-cells, and signaling through GPR109A inhibited glucose stimulated insulin secretion (GSIS). However, the expression of GPR109A in human islets and its functional relevance is still not known. Methods The expression of GPR109A was examined by antibody staining and in situ hybridization on pancreatic paraffin sections. GPR109A was cloned and expressed in INS-1 islet beta-cells. Intracellular cAMP and GSIS were determined using enzyme-linked immunosorbent assay (ELISA). Results The expression of GPR109A was confirmed in murine islet beta-cells and further detected in human counterparts by using commercially available polyclonal antibodies. In situ hybridization study detected the transcripts of GPR109A, but not that of closely related GPR109B. Furthermore, GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice as compared to their respective controls. Further, GPR109A levels in insulinoma were also reduced dramatically as compared to islets found in corresponding non-tumor normal tissues. Quantitative RT-PCR analysis demonstrated that GPR109A transcripts were severely down-regulated in rodent insulinoma cell lines as compared to that of freshly isolated islets from mice. Finally, human and murine GPR109A expression cassettes were transfected into INS-1 cells, which resulted in reduced accumulation of cAMP and insulin secretion after incubation with niacin. The effect could be completely abrogated by pretreatment with pertussis toxin. Conclusions These results demonstrate that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study.

Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, there is no general consensus as to which staging system is the most reliable for predicting the survival of patients with HCC. The aims of this study were to compare commonly-used staging systems in a cohort of Chinese HCC patients undergoing curative resection. Methods: From January 1991 to June 2002, 234 Chinese patients undergoing curative resection for HCC from one medical center were evaluated. All patients were classified by the Okuda, Cancer of the Liver Italian Program (CLIP), tumor node metastasis (TNM) (6th edition) and the Chinese University Prognostic Index (CUPI) staging systems. Survival curves were calculated using the Kaplan–Meier method and were examined using log-rank testing. The overall predictive power for patient survival with each staging system was evaluated by the area under the receiver operating characteristic (ROC) curve. Results: The overall median survival of the entire cohort was 24.9 months (95% confidence interval (CI) 18.15–31.65 months) and the estimated survival rates at 1, 3, and 5 years were 69.66% ± 3.01%, 41.02% ± 3.31%, and 29.08% ± 3.55%, respectively. In our patient cohort, the log-rank test demonstrated that the TNM and Okuda staging systems gave better results than the other staging systems in the prognosis stratification. The prognostic predictive powers of the TNM staging for survival, evaluated by ROC curve areas, was also superior. Conclusions: For HCC patients undergoing curative resection, the TNM staging system (6th edition) proved the best for prognostic stratification and prognosis prediction.

To compare imaging findings of CT and contrast-enhanced US (CEUS) in hepatic angiomyolipoma (HAML) and investigate their pathological correlations. Imaging findings and preoperative diagnosis of CT and CEUS were retrospectively compared head to head in 46 patients with 54 histologically proven HAMLs. Correlations between imaging features and preoperative diagnosis with pathological types of HAMLs were analyzed. Fat was detected in 100% of lipomatous type, 84.6% of mixed type, and 7.1% of myomatous type (p = 0.000) of HAML at unenhanced CT. Well-defined hyper-echogenicity was displayed in 100% of lipomatous type, 88.5% of mixed type, 50% of myomatous type, and 66.7% of angiomatous type of HAMLs at unenhanced US. More arterial hyper-enhancement was noted on CEUS (100%) than on CT (73.1%) in mixed type (p = 0.015) and in lipomatous type (90.9% vs. 9.1%, p = 0.000) of HAMLs. Washout was present in more HAMLs on CT than on CEUS (42.6% vs. 18.5%, p = 0.007). Correct preoperative diagnosis was suggested in more HAMLs of myomatous type on CEUS than on CT (42.9% vs. 0%, p = 0.016) but showed no difference in other types of HAMLs. There are considerable discrepancies between CT and CEUS findings of HAMLs, and the imaging appearance and preoperative diagnosis of HAMLs on CT and CEUS are significantly affected by pathological types of HAMLs.

Purpose: To investigate the factors that influence the enhancement patterns of intrahepatic cholangiocarcinomas (ICC) on contrast-enhanced ultrasound (CEUS) and analyze the correlations between the enhancement patterns on CEUS and pathological findings. Materials and Methods: Ninety-six patients with 96 pathologically confirmed ICCs underwent CEUS. CEUS images were retrospectively evaluated for tumor enhancement patterns in the arterial, portal and late phases. The arterial enhancement patterns were correlated with clinicopathological factors. The possible influencing factors were correlated with pathologic findings. Results: Thirty-six patients with ICC demonstrated rim-like enhancement, and 60 exhibited non-rim-like enhancement in the arterial phase on CEUS. The incidence of non-rim-like-enhancing ICCs was higher in patients with cirrhosis and chronic viral hepatitis than patients with no chronic liver disease (p = 0.001). The sizes of the ICCs with homogeneous hyper-enhancement were significantly smaller than those with inhomogeneous hyper-enhancement (p = 0.007). Arterial non-rim-like-enhancing ICCs showed higher microvessel density (MVD) and arterial density (AD) and less fibrous stroma and necrosis than rim-like-enhancing ICCs. Arterial inhomogeneous-enhancing ICCs had lower MVD and AD and much more fibrous stroma and necrosis than homogeneous-enhancing ICCs. Conclusion: The enhancement pattern of ICCs in the arterial phase on CEUS was affected by a liver cirrhosis and chronic viral hepatitis and tumor size. The amount of MVD, AD, fibrous stroma and necrosis in ICC tumors may be responsible for the difference in the enhancement patterns.

Objectives Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal tumor of the liver and its diagnosis has been considered challenging. The aim of this study was to investigate prospectively the diagnostic efficacy of the incorporation of both baseline ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of HAML in patients without cirrhosis. Materials and Methods Consecutive 1748 non-cirrhotic patients with focal liver lesions (FLLs) were prospectively enrolled. Baseline US and CEUS were performed before resection or biopsy. Ultrasound imaging diagnosis of FLLs was compared with the pathological results. Results Final diagnoses were established in 41 patients with HAML (2.3%) with normal alpha fetal protein (AFP) level and in 1707 patients with FLL other than HAML. Diagnostic criteria for HAML was based on the combination of baseline US and CEUS appearance of the nodule: (1) Well-defined, marked hyper-echoic nodule without surrounding hypo-echoic halo on baseline US; (2) hyper-enhancement in the arterial phase (exclude initial peripheral nodular enhancement and spoke-wheel arteries) and remains hyper-enhancement or iso-enhancement in the late phase. The diagnostic criteria were fulfilled in 31 HAMLs, 1 hepatocellular adenoma and 1 hemangioma. Ten HAMLs were misdiagnosed as other liver tumors because they did not meet the diagnostic criteria mentioned above and consequently yielded a sensitivity, specificity, positive predictive values, negative predictive values and Youden index of 75.61%, 99.88%, 93.94%, 99.42%, and 0.75 respectively. Conclusion The combination of baseline US and CEUS may lead to the correct diagnosis noninvasively in the majority of HAMLs in non-cirrhotic patients with normal AFP level.

Objectives To investigate the role of pericytes in constructing the malformed microvessels (MVs) and participating microvascular architecture heterogeneity of glioma. Methods Forty human glioma tissue samples (WHO grade II-IV) were included in present study. Observation of blood vessel patterns, quantitative analysis of endothelial cells (ECs)- and pericyte-labeled MVs and comparison between malignant grades based on single- or double-immunohistochemical staining. The MV number density (MVND), microvascular pericyte number density (MPND), and microvascular pericyte area density (MPAD) were calculated. The expression of PDGFβ was also scored after immunostaining. Results In grade II glioma, most of tumor MVs were the thin-wall CD34+ vessels with near normal morphology. In addition to thin-wall CD34+ MVs, more thick-wall MVs were found in grade III glioma, which often showed α-SMA positive. Most of MVs in grade IV glioma were in the form of plexus, curled cell cords and glomeruloid microvascular proliferation while the α-SMA+ cells were the main components. The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression. With the increase of glioma grades, the α-SMA+ MVND, CD34+ MVND and MPND were significantly augmented although the increase of CD34+ MVND but not MPAD was statistically insignificant between grade III and IV. It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis. The expression level of PDGFβ was upregulated and directly correlated with the MPND in different glioma grades. Conclusion Hyperplasia of pericytes was one of the significant characteristics of malignant glioma and locally proliferated pericytes were the main constituent of MVs in high grade glioma. The pathological characteristics of pericytes could be used as indexes of malignant grades of glioma.

To explore the effects of B-cell specific Maloney leukemia virus integration site 1 (Bmi1) gene on endothelial cells promoting glioma stem cell (GSC)-like phenotype.Glioblastoma cell line GL261 and brain micro-vessel endothelial cell line b.END3 were used. Transwell co-culture system, limit dilution assay, xenograft, real-time polymerase chain reaction (PCR), Western blot, fluorescence activating cell sorter (FACS) and gene knock-down assay were used to determine the GSC-like phenotype and Bmi1 gene expression in glioma cells.Compared with the control of GL261 cell alone, (1) more and larger tumor spheres formed after co-culturing with endothelial cells (62.5% ± 1.5% vs 25.0% ± 4.6% at 40 cells/well, P = 0.000). Xenografts generated by GL261 cells with b.END3 cells appeared earlier and were larger than that by GL261 cells alone ((0.798 ± 0.297) cm(3) vs (0.362 ± 0.123) cm(3), P = 0.000); (2) CD133 positive glioma cells increased after co-culturing with endothelial cells (8.48% ± 0.78% vs 4.81% ± 0.37%, P = 0.000); (3) the expression of Bmi1 in co-cultured glioma cells was up-regulated at mRNA level (2.72 ± 0.18 vs 1.00 ± 0.15, P = 0.000) and at protein level; (4) the above phenomenon was attenuated when Bmi1 gene expression was inhibited by siRNA in glioma cells, CD133 positive portion of Bmi1-knockdown GL261 cells co-culturing with b.END3 cells decreased than that of wildtype GL261 cells (0.34% ± 0.21% vs 1.70% ± 0.69%, P = 0.025).Endothelial cells promote GSC-like phenotype by up-regulating the expression of Bmi1 in glioma cells.

Object The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM). Methods This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages. Results Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons. Conclusions This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.

Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.

To investigate the related factors of portal vein tumor thrombosis (PVTT) in patients with HCC.A total number of 234 patients with hepatocellular carcinoma (HCC) were included in this retrospective study. Uni-variate and multi-variate logistic regression analysis were employed to analyze the association between PVTT and 18 routine clinical parameters.Among the 234 patients with HCC, 15% of patients (35/235) had PVTT. Univariate logistic regression analysis revealed significant association of age (P = 0.016), gamma glutamyl transferase (GGT, P = 0.003), number of segmental invasion (P = 0.007), microvascular invasion (P0.01), segment location of S2 (P = 0.001), S3 (P = 0.000), S4 (P = 0.004) and S6 (P = 0.016). Multivariate analysis shows potential significant predictors of PVTT in HCC were age (RR: 0.373; 95% CI: 0.146-0.954; P = 0.040), the tumor location of S3 (RR: 4.625; 95% CI: 1.916-11. 165;P = 0.001), GGT (RR: 4.091; 95% CI: 1.448-11.553; P = 0.008) and microvascular invasion (RR: 20.912; 95% CI: 4.745-92.172; P0.01).PVTT occurred more commonly in the younger (50 years old), and those with high level of GGT, segment location of S3 and microvascular invasion.

To investigate the clinical significance and prognostic value of the expression of DNA methyltransferase 1 (DNMT1) and human leukocyte antigen-DRalpha (HLA-DRalpha) in hepatocelluar carcinoma (HCC).Paraffin-embedded tissues of 234 HCC underwent curative liver resection and 18 healthy adult liver samples from January 1991 to June 2002 in our department were used for the tissue microarray. Immunohistochemical technique (EnVision) was applied to detect the expression of DNMT1 and HLA-DRalpha. The relationships between DNMT1, HLA-Ralpha and clinicopathological variables were analyzed statistically.The rates of positive expression of DNMT1 and HLA-DRalpha were 27.4% and 39.3%. The significant correlation was present between DNMT1 and portal vein tumor thrombus, alpha fetoprotein (AFP) level or TNM staging (P0.05), but no significant correlation was present between DNMT1 and lymph node invasion. The significant correlation was present between HLA-DRalpha and lymph node invasion or TNM staging (P0.05), but no significant correlation was present between HLA-DRalpha and lymph node invasion or AFP level (P0.05). The postoperative median survival time was 6.87 months and the 1-, 3-, 5-year cumulative survival rate was (38.89+/-6.63)%, (19.92+/-5.48)%, (17.58+/-5.31)% respectively in HCC with positive DNMT1, while the median survival time was 40.33 months and the 1-, 3-, 5-year cumulative survival rate was (81.01+/-4.41)%, (50.78+/-5.84)%, (38.04+/-6.09)% respectively in patients with negative DNMT1(P0.001). The postoperative median survival time was 40.33 months and the 1-, 3-, 5-year cumulative survival rate was (81.01+/-4.41)%, (50.78+/-5.84)%, (38.04+/-6.09)% respectively in HCC with positive HLA-DRalpha, while the median survival time was 12.43 months and the 1-, 3-, 5-year cumulative survival rate was (51.72+/-6.56)%, (26.44+/-5.91)%, (13.71+/-6.83)% (P0.01) respectively in patients with negative HLA-DRalpha (P0.001).DNMT1 and HLA-DRalpha are prognostic factors for HCC, which may be promising molecular prognostic factors for HCC.

To study the effects of celecoxib on the cell proliferation and expression of vascular endothelial growth factor (VEGF) in human nasopharyngeal carcinoma line.3-[ 4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) test was used to investigate the cell proliferation. Flow cytometry (FCM) was used to analyze the cell cycle arrest. Immunocytochemistry technique was to observe the expression of VEGF.Celecoxib inhibited the growth of nasopharyngeal carcinoma line, the cell number of G0/G1 phase increased from 62.13% to 91.35%, and the cell number of G2/M and S phase decreased from 21.59% to 3.56% and from 16.28% to 5.01%, respectively, cell cycle progression was arrested at G1/S phase. Celecoxib decreased the positive expression of VEGF in HNE-1 cells.Celecoxib inhibited the proliferation of nasopharyngeal carcinoma significantly and the expression of VEGF.

Inhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated.Thirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group: (A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on HE stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type III (Col-III) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-III deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system.The count of eosinophils in BALF (x 10(5)/ml) of group A and B were higher than that of group C and D (35.70 +/- 25.22, 11.49 +/- 5.51 vs. 1.00 +/- 0.90, 1.02 +/- 0.78, P0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95 +/- 2.28, 1.54 +/- 1.09 vs. 0.76 +/- 0.45, 0.88 +/- 0.25; medial airway: 9.22 +/- 3.89, 3.99 +/- 2.3 vs. 1.25 +/- 1.20, 0.64 +/- 0.36; small airway: 11.56 +/- 4.02, 2.67 +/- 1.15 vs. 1.32 +/- 0.83, 0.43 +/- 0.24, P0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122 +/- 22, 174 +/- 23 vs. 219 +/- 34, 229 +/- 20; small airway 135 +/- 29, 165 +/- 41 vs. 236 +/- 20, 220 +/- 16, P0.05), the difference between group A and B, group B and C was significant. The gray values of Col-III deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153 +/- 21, 174 +/- 22 vs. 189 +/- 14, 200 +/- 18; small airway 133 +/- 23, 176 +/- 20 vs. 191 +/- 14, 198 +/- 20, P0.05), the difference between group A and B was significant.Inhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.

Background Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study. Methods From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted. Results In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28–74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19–9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000). Conclusions The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.