Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents.

Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients. This is attained by elaborate crosstalk between Notch and NF-κB pathways. Mechanistically, Notch receptors activated by HTNV enhance NF-κB signaling by recruiting IKKß and p65, promoting inflammatory macrophage polarization in both species. However, in mice rather than humans, Notch-mediated inflammation is timely restrained by a series of murine-specific long noncoding RNAs transcribed by the Notch pathway in a negative feedback manner. Among them, the lnc-ip65 detaches p65 from the Notch receptor and inhibits p65 phosphorylation, rewiring macrophages from the pro-inflammation to the pro-resolution phenotype. Genetic ablation of lnc-ip65 leads to destructive HTNV infection in mice. Thus, our findings reveal an immune-braking function of murine noncoding RNAs, offering a special therapeutic strategy for HTNV infection.

Basal cell carcinoma arising within nevus sebaceous on the right scalp in a 55-year-old male: A case report and review of literature.

We report here a case of nevus sebaceous in a 55-year-old male, who presented with a 50-year history of an asymptomatic swelling in his right scalp. The solitary, yellowish, expansile plaque over the scalp gradually became lobulated and turned dark-pigmented with spontaneous bleeding, itching discomfort, and occasional ulceration after scratching. The male's clinical presentation and histopathological findings were compatible with basal cell carcinoma arising in nevus sebaceous. At present, 5-aminolevulinic acid photodynamic therapy (ALA-PDT) emerges as a novel treatment modality which has proved safe and effective. In this case, three sessions of photodynamic therapy in combination with surgical excision were performed, leaving mild pigmentation within 3 weeks. The patient showed good cosmetic outcome, minimal scarring on the right scalp without further complications, disease recurrence or metastasis after ALA-PDT within six months.

Application of myocardial work in predicting adverse events among patients with resistant hypertension.

BACKGROUND: Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths worldwide. Approximately 10-20% of all patients with hypertension and 15-18% of the general population who are treated for hypertension have resistant hypertension (RH). Patients with RH have a higher risk of end-organ damage, such as carotid intima-media thickening, retinopathy, left ventricular hypertrophy and heart failure, myocardial infarction, stroke, impaired renal function, and death than those with controlled blood pressure. In the present study, we applied echocardiography to patients with RH to evaluate myocardial work (MW) and determine whether it is predictive for the occurrence of adverse events within 3 years. METHODS: We included 283 outpatients and inpatients aged ≥ 18 years who met the clinical criteria for RH, without arrhythmia and severe aortic valve stenosis, between July 2018 and June 2019. The patients were followed up for 3 years from starting enrollment, and any adverse event that occurred during the period was used as the observation end point. Each enrolled patient underwent a complete transthoracic echocardiogram examination, blood pressure was measured and recorded, and MW was then analyzed. RESULTS: Eighty-two (28.98%) patients with RH had adverse events, such as myocardial infarction (n = 29, 35.36%), heart failure (n = 4, 0.05%), renal insufficiency (n = 40, 48.78%), renal failure (n = 2, 0.02%), cerebral infarction (n = 5, 0.06%), and cerebral hemorrhage (n = 2, 0.02%), and no death events occurred. In patients with RH and adverse events, global longitudinal strain (GLS) (- 16% vs. - 18%), the global work index (2079 mmHg% vs. 2327 mmHg%), global constructive work (2321 mmHg% vs. 2610 mmHg%), and global work efficiency (93% vs. 94%) were lower than those in patients without adverse events. However, global wasted work (GWW) was higher in patients with RH and adverse events than in those without adverse events (161 mmHg% vs. 127 mmHg%). GLS and GWW were the most significant in predicting adverse events. CONCLUSIONS: MW, especially GLS and GWW, is a good method to predict 3-year adverse events in patients with RH.

Globular adiponectin-mediated vascular remodeling by affecting the secretion of adventitial-derived tumor necrosis factor-α induced by urotensin II.

OBJECTIVES: In this study, we explored how adiponectin mediated urotensin II (UII)|-induced tumor necrosis factor-|α (TNF-|α) and α|-smooth muscle actin (α|-SMA) expression and ensuing intracellular signaling pathways in adventitial fibroblasts (AFs). METHODS: Growth-arrested AFs and rat tunica adventitia of vessels were incubated with UII and inhibitors of signal transduction pathways for 1|‒|24 h. The cells were then harvested for TNF-α receptor (TNF-|α-R) messenger RNA (mRNA) and TNF-|α protein expression determination by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Adiponectin and adiponectin receptor (adipoR) expression was measured by RT-PCR, quantitative real-time PCR (qPCR), immunohistochemical analysis, and cell counting kit-8 (CCK-8) cell proliferation experiments. We then quantified TNF-α and α-SMA mRNA and protein expression levels by qPCR and immunofluorescence (IF) staining. RNA interference (RNAi) was used to explore the function of the adipoR genes. To investigate the signaling pathway, we applied western blotting (WB) to examine phosphorylation of adenosine 5'-monophosphate (AMP)|-activated protein kinase (AMPK). In vivo, an adiponectin (APN)|-knockout (APN-KO) mouse model mimicking adventitial inflammation was generated to measure TNF-α and α|-SMA expression by application of qPCR and IF, with the goal of gaining a comprehensive atlas of adiponectin in vascular remodeling. RESULTS: In both cells and tissues, UII promoted TNF-α protein and TNF-α-R secretion in a dose- and time-dependent manner via Rho/protein kinase C (PKC) pathway. We detected marked expression of adipoR1, T-cadherin, and calreticulin as well as a moderate presence of adipoR2 in AFs, while no adiponectin was observed. Globular adiponectin (gAd) fostered the growth of AFs, and acted in concert with UII to induce α-SMA and TNF-α through the adipoR1/T-cadherin/calreticulin/AMPK pathway. In AFs, gAd and UII synergistically induced AMPK phosphorylation. In the adventitial inflammation model, APN deficiency up-regulated the expression of α-SMA, UII receptor (UT), and UII while inhibiting TNF-|α expression. CONCLUSIONS: From the results of our study, we can speculate that UII induces TNF|-|α protein and TNF-|α|-R secretion in AFs and rat tunica adventitia of vessels via the Rho and PKC signal transduction pathways. Thus, it is plausible that adiponectin is a major player in adventitial progression and could serve as a novel therapeutic target for cardiovascular disease administration.

Prognostic analysis of pT1-T2aN0M0 cervical adenocarcinoma based on random survival forest analysis and the generation of a predictive nomogram.

Background: The efficacy of adjuvant radiotherapy for postoperative patients with early-stage cervical adenocarcinoma who are lymph node-negative is still inconclusive. Establishing a nomogram to predict the prognosis of such patients could facilitate clinical decision-making. Methods: We recruited 4636 eligible patients with pT1-T2aN0M0 cervical adenocarcinoma between 2004 and 2016 from the Surveillance, Epidemiology and End Results (SEER) database. Random survival forest (RSF) and conditional survival forest (CSF) model was used to assess the prognostic importance of each clinical characteristic variable. We identified independent prognostic factors associated with overall survival (OS) by univariate and multivariate Cox regression risk methods and then constructed a nomogram. We stratified patients based on nomogram risk scores and evaluated the survival benefit of different adjuvant therapies. To reduce confounding bias, we also used propensity score matching (PSM) to match the cohorts before performing survival analyses. Results: The RSF and CSF model identified several important variables that are associated with prognosis, including grade, age, radiotherapy and tumor size. Patients were randomly divided into training and validation groups at a ratio of 7:3. Multivariate cox analysis revealed that age, grade, tumor size, race, radiotherapy and histology were independent prognostic factors for overall survival. Using these variables, we then constructed a predictive nomogram. The C-index value for evaluating the prognostic nomogram fluctuated between 0.75 and 0.91. Patients were divided into three subgroups based on risk scores, and Kaplan-Meier (K-M) survival analysis revealed that in the low-risk group, postoperative chemotherapy alone was associated with a significantly worse OS than surgery alone. Following PSM, survival analysis showed that compared with surgery alone, radiotherapy was associated with a worse OS in the training group although there was no significant difference in the validation group. Conclusions: For patients with pT1-T2aN0M0 cervical adenocarcinoma, adjuvant treatments such as postoperative radiotherapy or chemotherapy, compared with surgery alone, are of no benefit with regards to patient survival. Our prognostic nomogram exhibits high accuracy for predicting the survival of patients with early-stage postoperative cervical adenocarcinoma.

Cardiac angiosarcoma: A case report and review of the literature.

Primary cardiac tumors are extremely rare, among which malignancies comprise about 15-25%. As the most common type of primary cardiac malignancies, angiosarcomas tend to arise in the right heart, especially right atrium. In this case report, we presented a 32-year-old female with primary cardiac angiosarcoma in the right atrial appendage detected by transesophageal echocardiography, as it is difficult to display on conventional transthoracic echocardiography.

The Current State of Research Regarding the Role of Non-Coding RNAs in Cutaneous Squamous Cell Carcinoma.

Skin cancers, including those of both both melanoma and non-melanoma subtypes, remain among the most common forms of human cancer. Non-melanoma skin cancers are typically further differentiated into the basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC) categories. Current approaches to diagnosing and treating cSCC remain unsatisfactory, and the prognosis for patients with this disease is relatively poor. Recent advances in high-throughput sequencing have led to an increasingly robust understanding of the diversity of non-coding RNAs (ncRNAs) expressed in both physiological and pathological contexts. These ncRNAs include microRNAs, long ncRNAs, and circular RNAs, all of which have been found to play key functional roles and/or to have value as diagnostic biomarkers or therapeutic targets in a range of different disease contexts. The number of ncRNAs associated with cSCC continues to rise, and as such, there is clear value in comprehensively reviewing the functional roles of these molecules in this form of cancer in order to highlight future avenues for research and clinical development.

MD-NDNet: a multi-dimensional convolutional neural network for false-positive reduction in pulmonary nodule detection.

Pulmonary nodule false-positive reduction is of great significance for automated nodule detection in clinical diagnosis of low-dose computed tomography (LDCT) lung cancer screening. Due to individual intra-nodule variations and visual similarities between true nodules and false positives as soft tissues in LDCT images, the current clinical practices remain subject to shortcomings of potential high-risk and time-consumption issues. In this paper, we propose a multi-dimensional nodule detection network (MD-NDNet) for automatic nodule false-positive reduction using deep convolutional neural network (DCNNs). The underlying method collaboratively integrates multi-dimensional nodule information to complementarily and comprehensively extract nodule inter-plane volumetric correlation features using three-dimensional CNNs (3D CNNs) and spatial nodule correlation features from sagittal, coronal, and axial planes using two-dimensional CNNs (2D CNNs) with attention module. To incorporate different sizes and shapes of nodule candidates, a multi-scale ensemble strategy is employed for probability aggregation with weights. The proposed method is evaluated on the LUNA16 challenge dataset in ISBI 2016 with ten-fold cross-validation. Experiment results show that the proposed framework achieves classification performance with a CPM score of 0.9008. All of these indicate that our method enables an efficient, accurate and reliable pulmonary nodule detection for clinical diagnosis.

Chronic morphine induces cyclic adenosine monophosphate formation and hyperpolarization-activated cyclic nucleotide-gated channel expression in the spinal cord of mice.

Chronic morphine exposure persistently activates Gαi/o protein-coupled receptors and enhances adenylyl cyclase (AC) activity, which can increase cyclic adenosine monophosphate (cAMP) production. Direct binding of cAMP to the cytoplasmic site on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels increases the probability of channel opening. HCN channels play a prominent role in chronic pain the disease that shares some common mechanisms with opioid tolerance. This compensatory AC activation may be responsible for the induction of morphine-induced analgesic tolerance. We investigated spinal cAMP formation and expression of HCN2 in the spinal cord, and observed the effect of AC inhibition on the induction of morphine analgesic tolerance. We found that chronic morphine-induced antinociceptive tolerance increased spinal cAMP formation and the expression of spinal HCN2. Inhibition of spinal AC partially blocked chronic morphine-induced cAMP formation and prevented the induction of morphine-induced analgesic tolerance. Inhibition of HCN2 also showed a partial preventive effect on morphine-induced tolerance, hypothermia tolerance and also the right-shift of the dose-response curve. We conclude that repeated morphine treatment increases AC activity and cAMP formation, and also spinal HCN2 expression, blockade of AC or HCN2 can prevent the development of morphine-induced analgesic tolerance.

Weakly-supervised convolutional neural networks of renal tumor segmentation in abdominal CTA images.

BACKGROUND: Renal cancer is one of the 10 most common cancers in human beings. The laparoscopic partial nephrectomy (LPN) is an effective way to treat renal cancer. Localization and delineation of the renal tumor from pre-operative CT Angiography (CTA) is an important step for LPN surgery planning. Recently, with the development of the technique of deep learning, deep neural networks can be trained to provide accurate pixel-wise renal tumor segmentation in CTA images. However, constructing the training dataset with a large amount of pixel-wise annotations is a time-consuming task for the radiologists. Therefore, weakly-supervised approaches attract more interest in research. METHODS: In this paper, we proposed a novel weakly-supervised convolutional neural network (CNN) for renal tumor segmentation. A three-stage framework was introduced to train the CNN with the weak annotations of renal tumors, i.e. the bounding boxes of renal tumors. The framework includes pseudo masks generation, group and weighted training phases. Clinical abdominal CT angiographic images of 200 patients were applied to perform the evaluation. RESULTS: Extensive experimental results show that the proposed method achieves a higher dice coefficient (DSC) of 0.826 than the other two existing weakly-supervised deep neural networks. Furthermore, the segmentation performance is close to the fully supervised deep CNN. CONCLUSIONS: The proposed strategy improves not only the efficiency of network training but also the precision of the segmentation.

Temporally downsampled cerebral CT perfusion image restoration using deep residual learning.

PURPOSE: Acute ischemic stroke is one of the most causes of death all over the world. Onset to treatment time is critical in stroke diagnosis and treatment. Considering the time consumption and high price of MR imaging, CT perfusion (CTP) imaging is strongly recommended for acute stroke. However, too much CT radiation during CTP imaging may increase the risk of health problems. How to reduce CT radiation dose in CT perfusion imaging has drawn our great attention. METHODS: In this study, the original 30-pass CTP images are downsampled to 15 passes in time sequence, which equals to 50% radiation dose reduction. Then, a residual deep convolutional neural network (DCNN) model is proposed to restore the downsampled 15-pass CTP images to 30 passes to calculate the parameters such as cerebral blood flow, cerebral blood volume, mean transit time, time to peak for stroke diagnosis and treatment. The deep restoration CNN is implemented simply and effectively with 16 successive convolutional layers which form a wide enough receptive field for input image data. 18 patients' CTP images are employed as training set and the other six patients' CTP images are treated as test dataset in this study. RESULTS: Experiments demonstrate that our CNN can restore high-quality CTP images in terms of structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR). The average SSIM and PSNR for test images are 0.981 and 56.25, and the SSIM and PSNR of regions of interest are 0.915 and 42.44, respectively, showing promising quantitative level. In addition, we compare the perfusion maps calculated from the restored images and from the original images, and the average perfusion results of them are extremely close. Areas of hypoperfusion of six test cases could be detected with comparable accuracy by radiologists. CONCLUSION: The trained model can restore the temporally downsampled 15-pass CTP to 30 passes very well. According to the contrast test, sufficient information cannot be restored with, e.g., simple interpolation method and deep convolutional generative adversarial network, but can be restored with the proposed CNN model. This method can be an optional way to reduce radiation dose during CTP imaging.

Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia.

BACKGROUND AND PURPOSE: The P2X3 receptor is a major receptor in the processing of nociceptive information in dorsal root ganglia. We investigated the role of the P2X3 receptor and the detailed mechanisms underlying chronic morphine-induced analgesic tolerance in rats. EXPERIMENTAL APPROACH: Repeated i.t. morphine treatment was used to induce anti-nociceptive tolerance. The expression of spinal P2X3 receptor, phosphorylated PKCε and exchange factor directly activated by cAMP (Epac) were evaluated. Effects of A-317491 (P2X3 antagonist), ε-V1-2 (PKCε inhibitor) and ESI-09 (Epac inhibitor) on mechanical pain thresholds and tail-flick latency after chronic morphine treatment were determined. Co-localization of P2X3 receptor with NeuNs (marker of neuron), IB4 (marker of small DRG neurons), peripherin, PKCε and Epac were performed by double immunofluorescence staining. KEY RESULTS: Chronic morphine time-dependently increased the expression of P2X3 receptor, phosphorylated PKCε and Epac in DRGs. ε-V1-2 prevented chronic morphine-induced expression of P2X3 receptor. ESI-09 decreased the phosphorylation of PKCε and up-regulated expression of Epac after chronic morphine exposure. Mechanical pain thresholds and tail-flick latency showed that A317491, ε-V1-2 and ESI-09 significantly attenuated the loss of morphine's analgesic potency. Morphine-induced P2X3 receptor expression mainly occurred in neurons staining for IB4 and peripherin. Co-localization of P2X3 receptor with PKCε and Epac was demonstrated in the same neurons. CONCLUSIONS AND IMPLICATIONS: Chronic morphine exposure increased the expression of P2X3 receptor, and i.t. P2X3 receptor antagonists attenuated the loss of morphine's analgesic effect. Inhibiting Epac/PKCε signalling was shown to play a significant inhibitory role in chronic morphine-induced P2X3 receptor expression and attenuate morphine-induced tolerance.

miR­24 may be a negative regulator of menin in lung cancer.

The incidence of lung cancer in China increases annually, and effective targets for the diagnosis and treatment of lung cancer are urgently needed. miRNAs are currently considered to be involved in the regulation of tumor development and growth. miR­24 has been found to contribute to the development of several tumors. Menin is a key tumor suppressor gene, and its expression is generally low in lung cancer. The effects of miR­24 on the biological behavior of lung cancer cells were detected by MTT and Transwell assays. In the present study, miR­24 was found to be associated with menin, affecting the activity of the SMAD3 pathway in lung cancer by inhibiting menin expression. miR­24 may promote the growth and metastasis and inhibit the apoptosis of lung cancer cells by targeting menin. Therefore, the aim of the present study was to provide a new theoretical basis for the targeted therapy of lung cancer.

Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation, Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts.

Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs). We also explored possible mechanisms of keloid pathogenesis. Primary fibroblast cultures were established from foreskin biopsies and skin biopsies from patients with keloids. The expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR, immunofluorescence staining, and immunohistochemical analysis. Next, KFs and normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used to examine cell proliferation and migration. The level of the collagen I, fibronectin (FN) and α-smooth muscle actin (α-SMA) mRNAs and proteins were determined by quantitative real-time RT-PCR and western blotting. The effects of RNA interference (RNAi) targeting the adipoR genes were detected. Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase-protein kinase (PI3K-Akt) were examined by western blotting to further investigate the signalling pathways. Furthermore, inhibitors of signal transduction pathways were investigated. The expression levels of adiponectin and adipoRs were significantly decreased in keloids compared with those in normal skin tissue. Adiponectin suppressed the CTGF-induced KFs, but not NFs, proliferation, migration and ECM production. Moreover, adiponectin inhibited the phosphorylation of AMPK, p38 and extracellular-regulated kinase (ERK), but not that of Jun N-terminal kinase (JNK) or Akt, in CTGF-treated KFs. The activity of adiponectin-mediated signalling pathways was attenuated by small interfering RNAs (siRNAs) targeting adipoR1 (but not siRNAs targeting adipoR2, T-cadherin or calreticulin), AMPK (Compound C), p38 (SB203580) inhibitors, and mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059). Based on our results, adiponectin suppresses CTGF-induced KFs proliferation, migration and ECM overproduction. One of the underlying mechanisms is the activation of the adipoR1, AMPK, p38, and ERK signalling pathways. Therefore, adiponectin may play an important role in the progression of keloids, suggesting a potential novel target for keloid treatment.

Comparative study of cisplatin-based definitive concurrent chemoradiotherapy with S-1 versus paclitaxel for unresectable locally advanced esophageal squamous cell carcinoma.

This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.

The association between aquaporin-1 expression, microvessel density and the clinicopathological features of hepatocellular carcinoma.

The present study aimed to evaluate the effects of aquaporin-1 (AQP1) level and intratumoral microvessel density (IMD) on the clinicopathological features of patients with hepatocellular carcinoma (HCC). The AQP1 expression levels, IMD and AQP1/IMD ratios in patients with HCC were measured using a semi-quantitative immunohistochemical technique. The association between these features and clinicopathological variables were evaluated. The prognostic impact of AQP1 and IMD on overall survival (OS), and 5-year disease-free survival (DFS) of HCC patients was investigated retrospectively. P<0.05 was considered to indicate a statistically significant difference. A total of 90 cases of HCC were included in the present study. AQP1 was markedly expressed in the membranes of microvessels and small vessels, but seldom in hepatocellular carcinoma cells. Blood vessels in the tumors were markedly stained by anti-cluster of differentiation 34 antibody. AQP1 expression and IMD was significantly correlated with tumor size, histologic grade, Child-Pugh classification, microvascular invasion and tumor-node-metastasis (TNM) stage (P<0.05). Concurrently, for the 5-year DFS and OS, a larger tumor size, poorly differentiated histological grade, B and C Child-Pugh classification, presence of microvascular invasion, high TNM stage, a high AQP1 expression and a high IMD were significant risk factors for mortality. Multivariate analysis revealed that TNM stage and IMD were independent unfavorable prognostic markers for 5-year DFS (P=0.049 and P=0.025, respectively) and OS (P=0.043 and P=0.042, respectively). These data suggest that high AQP1 expression and IMD are associated with tumor progression and prognosis in HCC. The IMD level may serve as an independent indicator for the 5-year DFS and OS.

Improving Low-dose Cardiac CT Images based on 3D Sparse Representation.

Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

Decreased expression of Sushi Domain Containing 2 correlates to progressive features in patients with hepatocellular carcinoma.

BACKGROUND: Sushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer. Increasing evidence suggests that SUSD2 plays a key role in tumorigenesis. However, the SUSD2 expression status and its functions in hepatocellular carcinoma (HCC) are still unrevealed. In the present study, we intended to investigate SUSD2 expression status and its correlation with the clinicopathological features in HCC patients. Furthermore,we examined the influence of SUSD2 on the proliferation, apoptosis, invasion and migration of the HCC cell lines HepG2 and SMMC7721. METHODS: We evaluated the SUSD2 expression in HCC tissues and paired normal liver tissues by quantitative real-time PCR and western blotting analysis. The clinicopathological significance of SUSD2 was investigated by immunohistochemistry (IHC) on a HCC tissue microarray. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of SUSD2. The correlation between SUSD2 protein expression and clinicopathological features of HCC was analyzed by Chi square test. The cell proliferation, apoptosis, invasion and migration potential were observed to detect the functions of SUSD2 in HCC cells. RESULTS: Decreased expression of SUSD2 mRNA and protein were observed in the majority of HCC tissues, compared with paired normal liver tissues. When SUSD2 high expression percentage was determined to be above 52.5 % (area under ROC curve = 0.769, P = 0.000), low expression of SUSD2 was observed in 62.2 % (112/180) of HCC tissues and high expression of SUSD2 was observed in all normal liver tissues (16/16) by IHC. Decreased expression of SUSD2 in patients was correlated with high histological grade (χ(2) = 5.198, P = 0.023), advanced clinical stage (χ(2) = 30.244, P = 0.000), pT status (χ(2) = 33.175, P = 0.000), pN status (χ(2) = 4.785, P = 0.029), pM status (χ(2) = 4.620, P = 0.032). Down-regulation of SUSD2 promoted cell proliferation,invasion and migration,reduced the cell apoptosis. CONCLUSIONS: Our findings suggest that SUSD2 may play as a tumor suppressor in HCC cells and could be served as an additional potential marker for diagnosis.

Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.

PURPOSE: This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) and to explore its potential correlation with the progression of NSCLC. METHODS: Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs). Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis. RESULTS: Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR), VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced (TGFBI) and proliferating cell nuclear antigen (PCNA) were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation. CONCLUSION: EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.

Does ligand-receptor mediated competitive effect or penetrating effect of iRGD peptide when co-administration with iRGD-modified SSL?

Ligand-mediated targeting of anticancer therapeutic agents is a useful strategy for improving anti-tumor efficacy. It has been reported that co-administration of a tumor-penetrating peptide iRGD (CRGDK/RGPD/EC) enhances the efficacy of anticancer drugs. Here, we designed an experiment involving co-administration of iRGD-SSL-DOX with free iRGD to B16-F10 tumor bearing mice to examine the action of free iRGD. We also designed an experiment to investigate the location of iRGD-modified SSL when co-administered with free iRGD or free RGD to B16-F10 tumor bearing nude mice. Considering the sequence of iRGD, we selected the GPDC, RGD and CRGDK as targeting ligands to investigate the targeting effect of these peptides compared with iRGD on B16-F10 and MCF-7 cells, with or without enzymatic degradation. Finally, we selected free RGD, free CRGDK and free iRGD as ligand to investigate the inhibitory effect on RGD-, CRGDK- or iRGD-modified SSL on B16-F10 or MCF-7 cells. Our results indicated that iRGD targeting to tumor cells was ligand-receptor mediated involving RGD to αv-integrin receptor and CRGDK to NRP-1 receptor. Being competitive effect, the administration of free iRGD would not be able to further enhance the anti-tumor activity of iRGD-modified SSL. There is no need to co-administrate of free iRGD with the iRGD-modified nanoparticles for further therapeutic benefit.