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Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole (ABZ) kills nematode larvae in the brain. However, dead larvae can trigger a severe inflammatory response, resulting in brain damage. Accumulating evidence suggests that calycosin represents a potential anti-inflammatory therapeutic candidate. In this study, we investigated the combined effects of ABZ and calycosin in angiostrongyliasis caused by A. cantonensis in BALB/c mice. Inflammatory mediators (such as phospho-nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinase-9, tumour necrosis factor-α and interleukin-1β) are associated with the development of meningitis and immune inflammatory reactions. We found that A. cantonensis significantly induces inflammatory mediator production and increases the blood–brain barrier (BBB) permeability. However, co-administration of both ABZ and calycosin markedly suppressed meningitis and inflammatory mediator production and decreased the BBB permeability compared to treatment with a single drug. Furthermore, calycosin and ABZ plus calycosin treatment facilitated production of the antioxidant haem oxygenase-1 (HO-1). Moreover, co-therapy with ABZ and calycosin failed to mitigate angiostrongyliasis in the presence of tin-protoporphyrin IX, an HO-1-specific inhibitor. This finding suggests that the beneficial effects of ABZ plus calycosin treatment on the regulation of inflammation are mediated by the modulation of HO-1 activation. The present results provide new insights into the treatment of human angiostrongyliasis using co-therapy with ABZ and calycosin.

Backgroud Toxocara canis, a source of visceral larva migrans, causes toxocariasis and induces respiratory symptoms. The reasons by which the pulmonary pathological alteration in the lungs infected with T. canis remain unclear. Methods The involvement of the pulmonary pathological alteration by histology, enzyme activity, and western blot analysis in the lungs of BALB/c mice after the infection of 2,000 embryonated eggs. Results The pathological effects gradually increased after the infection culminated in severe leukocyte infiltration and hemorrhage from days 4 to 14 post-inoculation. Gelatin zymography using substrate showed that the relative activity of matrix metalloproteinase (MMP) -9 and MMP-2 significantly increased in T. canis-infected mice. Western blot analysis indicated that the MMPs protein level of fibronectin monomer significantly increased in T. canis-infected mice compared with that in uninfected control. T. canis larvae mainly initiated leukocyte infiltration and hemorrhage in the lungs. Conclusion These phenomena subsequently induced the activities of MMPs in parallel with the pathological changes in early stage pulmonary inflammation. In conclusion, T. canis larval migration activated the MMPs and caused pulmonary pathogenesis.

Compared with MR plain scanning, gadolinium (Gd)-enhanced MR scanning can provide more diagnostic information. Gadopentetate dimeglumine is generally used as an MR enhancement contrast agent in some countries. It is a member of linear Gd-based contrast agents (GBCAs) which are considered more likely to release free Gd ions (Gd

Ischemic stroke is characterized by the loss of cerebral blood flow, which frequently leads to neurological deficits. Tissue plasminogen activator is the only therapeutic agent approved to treat ischemic stroke but increases the risk of intracranial hemorrhage and mortality. The fibrinogen-depleting agent lumbrokinase has been used to improve myocardial perfusion in symptomatic stable angina and to prevent secondary ischemic stroke. Lumbrokinase is highly fibrin-specific and only active in the presence of fibrin. Therefore, lumbrokinase has a low risk of hemorrhage due to excessive fibrinolysis. In this study, we aimed to clarify the neuroprotection of lumbrokinase in mice subjected to permanent middle cerebral artery occlusion. Lumbrokinase significantly attenuated infarct volume and improved neurological dysfunction. Lumbrokinase dramatically decreased the expressions of the endoplasmic reticulum (ER) transmembrane receptor protein inositol-requiring enzyme-1 (IRE1) and its downstream transcription factor, XBP-1, caspase-12, and NF-κB activity, thereby significantly inhibiting apoptosis and autophagy and decreasing the NLRP3 inflammasome. Our evidence indicates that post-stroke treatment with lumbrokinase protects against ischemic stroke, thereby regulating ER stress through the collective inhibitory effect of the IRE1 signaling pathways to decrease apoptosis, autophagy, and inflammatory responses. We suggest that lumbrokinase is potential as an adjuvant treatment for ischemic stroke.

Background Ischemic stroke is characterized by the loss of cerebral blood flow, which frequently leads to neurological deficits. Therefore, minimizing post-stroke functional disability is an important research topic. The fibrinogen-depleting agent lumbrokinase has been used to improve myocardial perfusion in symptomatic stable angina and to prevent secondary ischemic stroke. In this study, we aimed to clarify the neuroprotection of lumbrokinase on ischemic stroke and whether improve neurological dysfunction. We explored the neuroprotection and the underlying mechanisms of lumbrokinase in C57BL/6 mice subjected to permanent middle cerebral artery occlusion. Results Lumbrokinase at 1 mg/kg significantly attenuated the infarct volume and improved the neurological dysfunction. Lumbrokinase dramatically decreased the expressions of the endoplasmic reticulum (ER) transmembrane receptor protein inositol-requiring enzyme-1 (IRE1) and its downstream transcription factor, X-box binding protein-1, caspase-12, and nuclear factor kappa B activity. Moreover, lumbrokinase significantly inhibited apoptosis and autophagy and decreased the expression levels of the NOD-like receptor 3 inflammasome, caspase-1, and interleukin-1β compared with the vehicle treatment. Conclusions We suggest that post-stroke treatment with lumbrokinase protects against ischemic stroke by regulating ER stress through the IRE1 signaling pathways to inhibit apoptosis, autophagy, and inflammatory responses.

In ocular toxocariasis, Toxocara canis-induced inflammatory reaction can lead to eye destruction and granuloma, which is formed by immune cell infiltration and concurrent extensive remodeling tissue. Herein, the histomorphology of granuloma and proteinase production in the eye of T. canis-infected BALB/c mice were investigated. Pathological effects substantially increased after the infection culminated in a severe leukocyte infiltration and granuloma formation from days 4 to 56 post-inoculation. The matrix metalloproteinase (MMP)-2 and MMP-9 activities remarkably increased, compared with those of uninfected control, by gelatin zymography and Western blot analysis in ocular toxocariasis. Granuloma formation had a remarkably positive correlation with MMP-2 and MMP-9 levels. We suggested that T. canis larvae and leukocytes infiltrated from blood vessel both migrated into corpus adiposum orbitae. Activated leukocytes secreted MMP-2 and MMP-9, leading to fibronectin degradation. The imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 may play a role in inflammatory cell infiltration and extracellular matrix degradation, forming granuloma, in ophthalmological pathogenesis of T. canis infection.

Peroxisome-proliferator activator receptor γ (PPARγ) has an anti-inflammatory role that inhibits the nuclear factor-κB (NF-κB) pathway and regulates the expressions of pro-inflammatory proteins, whereas its role in parasitic meningoencephalitis remains unknown. In this study we investigated the role of PPARγ and related mechanisms in eosinophilic meningoencephalitis caused by the rat lungworm Angiostrongylus cantonensis. We observed increased protein NF-κB expression in mouse brain tissue using GW9662, which is the specific antagonist of PPARγ, in a mouse model of angiostrongyliasis. Then we investigated NF-κB-related downstream proteins, such as COX-2, NOSs, and IL-1β, with Western blot or enzyme-linked immunosorbent assay and found that the protein expression was upregulated. The results of gelatin zymography also showed that the MMP-9 activities were upregulated. Treatment with GW9662 increased the permeability of the blood-brain barrier and the number of eosinophils in cerebrospinal fluid. These results suggested that in angiostrongyliasis, PPARγ may play an anti-inflammation role in many inflammatory mediators, including NOS-related oxidative stress, cytokines, and matrix metalloproteinase cascade by decreasing the NF-κB action.

The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes eosinophilic meningitis or meningoencephalitis. Heme oxygenase 1 (HO-1) has several cytoprotective properties such as anti-oxidative, anti-inflammatory, and anti-apoptotic effects. HO-1 in brain tissues was induced in A. cantonensis-infected group and showed positive modulation in cobalt protoporphyrin (CoPP)-treated groups. Assay methods for the therapeutic effect include western blot analysis, enzyme-linked immunosorbent assay, gelatin zymography, blood-brain barrier permeability evaluation and eosinophil count in cerebrospinal fluid. The combination of albendazole (ABZ) and CoPP significantly decreased pro-inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-5, and IL-33 but significantly increased anti-inflammatory cytokines IL-10 and transforming growth factor-β. In addition, worm recovery, matrix metalloproteinase-9, BBB permeability, and eosinophil counts were decreased in the ABZ and CoPP co-treated groups. Induction of HO-1 with CoPP strongly inhibited the protein levels of caspase-3 and increased the induction of annexin-V and B-cell leukemia 2. Thus, co-treatment with ABZ and CoPP prevented A. cantonensis-induced eosinophilic meningoencephalitis and its anti-apoptotic effect by promoting HO-1 signaling prior to BBB dysfunction. HO-1 induction might be a therapeutic modality for eosinophilic meningoencephalitis.

Angiostrongylus cantonensis causes a human central nervous system (CNS) infection characterized by eosinophilic meningitis or meningoencephalitis. Individuals infected with A. cantonensis exhibit unbalanced walking. The mechanism of extensive neurological impairments of hosts caused by A. cantonensis larvae remains unclear. Tight junction proteins (e.g., claudin-5 and zonula occludens-1) are the most important regulators of paracellular permeability and cellular adhesion. In a previous study, we found that increased matrix metalloproteinase-9 (MMP-9) activity may be associated with blood-CNS barrier disruption and/or the degeneration of Purkinje cells in eosinophilic meningitis caused by A. cantonensis. In the present study, the co-localization of MMP-9 and tight junction proteins on the degeneration of Purkinje cells was measured via confocal laser scanning immunofluorescence microscopy. The statistical evidence indicated that MMP-9 correlated between tight junction protein disruption and Purkinje cell degeneration at 20 days post-infection with A. cantonensis. In conclusion, Purkinje cell degeneration is highly correlated with tight junction protein disruption via the MMP-9 activation pathway.

Circular RNAs were known to play vital role in myocardial ischemia reperfusion injury (MIRI), while the role of CircZNF609 in MIRI remains unclear. This study was aimed to investigate the function of CircZNF609 in MIRI.Hypoxia/reoxygenation (H/R) model was established to mimic MIRICircZNF609 was upregulated in H/R model. Inhibition of CircZNF609 alleviated H/R induced apoptosis, ROS generation, restored cell proliferation in cardiomyocytes and human umbilical vein endothelial cells. Mechanically, CircZNF609 directly sponged miR-214-3p to release PTGS2 expression. Functional rescue experiments showed that miR-214-3p/PTGS2 axis was involved in the function of circZNG609 in H/R model. Furthermore, data in mouse model revealed that knockdown of CircZNF609 significantly reduced the area of myocardial infarction and decreased myocardial cell apoptosis.CircZNF609 aggravated the progression of MIRI via targeting miR-214-3p/PTGS2 axis, which suggested CircZNF609 might act as a vital modulator in MIRI.

Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti-inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP-2 and/or MMP-9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 μM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 μM naringenin. Zymography analysis also revealed that the activities of MMP-2 and MMP-9 of GBM cells were significantly inhibited in response to 100, 200, or 300 μM naringenin treatment. Proteins of MMP-2 and MMP-9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.

Preoperative portal vein embolization (PVE) is employed clinically to avoid postoperative liver insufficiency. Animal models are usually used to study PVE in terms of mechanisms and pathophysiological changes. PVE is formerly monitored by conventional absorption contrast imaging (ACI) with iodine contrast agent. However, the side effects induced by iodine can give rise to animal damage and death. In this study, the feasibility of using phase contrast imaging (PCI) to show PVE using homemade CO2microbubbles in living rats has been investigated. CO2gas was first formed from the reaction between citric acid and sodium bicarbonate. The CO2gas was then encapsulated by egg white to fabricate CO2microbubbles. ACI and PCI of CO2microbubbles were performed and comparedin vitro. An additional increase in contrast was detected in PCI. PCI showed that CO2microbubbles gradually dissolved over time, and the remaining CO2microbubbles became larger. By PCI, the CO2microbubbles were found to have certain stability, suggesting their potential use as embolic agents. CO2microbubbles were injected into the main portal trunk to perform PVE in living rats. PCI exploited the differences in the refractive index and facilitated clear visualization of the PVE after the injection of CO2microbubbles. Findings from this study suggest that homemade CO2microbubbles-based PCI is a novel modality for preclinical PVE research.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta 1 (TGF-β1) superfamily that reverses age-related cardiac hypertrophy, improves muscle regeneration and angiogenesis, and maintains progenitor cells in injured tissue. Recently, targeted myocardial delivery of the GDF11 gene in aged mice was found to reduce heart failure and enhance the proliferation of cardiac progenitor cells after myocardial ischemia-reperfusion (I-R). No investigations have as yet explored the cardioprotective effect of exogenous recombinant GDF11 in acute I-R injury, despite the convenience of its clinical application. We sought to determine whether exogenous recombinant GDF11 protects against acute myocardial I-R injury and investigate the underlying mechanism in Sprague-Dawley rats. We found that GDF11 reduced arrhythmia severity and successfully attenuated myocardial infarction; GDF11 also increased cardiac function after I-R, enhanced HO-1 expression and decreased oxidative damage. GDF11 activated the canonical TGF-β signaling pathway and inactivated the non-canonical pathways, ERK and JNK signaling pathways. Moreover, administration of GDF11 prior to reperfusion protected the heart from reperfusion damage. Notably, pretreatment with the activin-binding protein, follistatin (FST), inhibited the cardioprotective effects of GDF11 by blocking its activation of Smad2/3 signaling and its inactivation of detrimental TGF-β signaling. Our data suggest that exogenous GDF11 has cardioprotective effects and may have morphologic and functional recovery in the early stage of myocardial I-R injury. GDF11 may be an innovative therapeutic approach for reducing myocardial I-R injury.

Irradiation has been found to increase TTo explore how nasopharyngeal irradiation affected SI changes on unenhanced TSingle-center, retrospective, case-control study.In all, 132 subjects: 66 NPM patients, 66 matched controls.1.5T and 3T/TRadiation doses (RDs) were calculated by a radiotherapy technician. SIs were measured by a radiologist. The DN-to-cerebellar white matter (CWM) SI ratios and their relative percentage change (RShapiro-Wilk test, paired t-test, independent t-test, Mann-Whitney U-test, Pearson and Spearman correlation.DN/CWMNasopharyngeal irradiation appeared to increase SI in T3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:250-259.

Peroxisome proliferator-activated receptor gamma (PPARγ) regulates neuroinflammation, and its agonists act as neuroprotective agents. This study aims to investigate the correlation between PPARγ and proinflammatory enzyme expression in astroglia infected with Toxoplasma gondii tachyzoite in vitro. Our results showed that matrix metalloprotease (MMP)-2, MMP-9, cyclooxygenase-2 (COX-2), prostaglandin (PGE)-2, inducible nitric-oxide synthase (iNOS), and nitric oxide (NO) were significantly increased in T. gondii-infected astroglia. Furthermore, the expression levels of MMP-2, MMP-9, COX-2, PGE-2, iNOS, and NO were significantly decreased by rosiglitazone-a PPARγ agonist. By contrast, the treatment with GW9662, a PPARγ antagonist, efficiently increased the expression levels of MMP-2, MMP-9, COX-2, PGE-2, iNOS, and NO. These results suggested that the treatment with rosiglitazone offers a potential strategy for controlling the inflammatory factors in T. gondii infection.

Background: Osteosarcoma is one of the most malignant cancers in children. Naringenin exhibits several cellular functions. Objectives: In this study, we investigate the effects of naringenin on osteosarcoma. Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect the cell viability. Zymography assay and transwell assay were used to measure the matrix metalloproteinase (MMP) activity and migration ability. Western blot analysis was used to determine the expression of migration-related proteins. Results: No overt alternation of cytotoxicity in response to different concentrations of naringenin for 24 h was found by MTT assay. MMP-2 and MMP-9 activities and expression were significantly repressed by naringenin in a dose-dependent manner, as evidenced by zymography and Western blot analysis. Naringenin dose dependently reduced the expression of mesenchymal marker Snail. Conclusion: These results indicate that naringenin exhibited antimigration property through inhibition of MMP-2 and MMP-9 and downregulation of Snail expression. Thus, naringenin may be a potential inhibitor of metastasis of osteosarcoma.

The objective of this study was to investigate the potential of hydrogen peroxide-generated oxygen gas-based phase contrast imaging (PCI) for visualizing mouse hepatic portal veins. The O2gas was made from the reaction between H2O2and catalase. The gas production was imaged by PCI in real time. The H2O2was injected into the enteric cavity of the lower sigmoid colon to produce O2in the submucosal venous plexus. The generated O2gas could be finally drained into hepatic portal veins. Absorption contrast imaging (ACI) and PCI of O2-filled portal veins were performed and compared. PCI offers high resolution and real-time visualization of the O2gas production. Compared with O2-based ACI, O2-based PCI significantly enhanced the revealing of the portal veinin vivo. It is concluded that O2-based PCI is a novel and promising imaging modality for future studies of portal venous disorders in mice models.

Portal vein imaging is an important method for investigating portal venous disorders. However, the diagnostic requirements are not usually satisfied when using single imaging techniques. Diagnostic accuracy can be improved by combining different imaging techniques. Contrast agents that can be used for combined imaging modalities are needed. In this study, the feasibility of using microbubbles containing gadolinium (MCG) as contrast agents for both phase contrast imaging (PCI) and magnetic resonance imaging (MRI) are investigated. MCG were made by encapsulating sulfur hexafluoride (SF6) gas with gadolinium and lyophilized powder. Absorption contrast imaging (ACI) and PCI of MCG were performed and comparedin vitro. MCG were injected into the main portal trunk of living rats. PCI and MRI were performed at 2 min and 10 min after MCG injection, respectively. PCI exploited the differences in the refractive index and visibly showed the MCG, which were not detectable by ACI. PCI could facilitate clear revelation of the MCG-infused portal veins. The diameter of the portal veins could be determined by the largest MCG in the same portal vein. The minimum diameter of clearly detected portal veins was about 300 µm by MRI. These results indicate that MCG could enhance both PCI and MRI for imaging portal veins. The detection sensitivity of PCI and MRI could compensate for each other when using MCG contrast agents for animals.

Preoperative portal vein embolization (PVE) is employed clinically to avoid postoperative liver insufficiency. Animal models are usually used to study PVE in terms of mechanisms and pathophysiological changes. PVE is formerly monitored by conventional absorption contrast imaging (ACI) with iodine contrast agent. However, the side effects induced by iodine can give rise to animal damage and death. In this study, the feasibility of using phase contrast imaging (PCI) to show PVE using homemade CO

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection.

Objective To provide a retrospective assessment of clinical characteristics of the patients with gastric glomus tumors and the imaging features of the tumors on multidetector row computed tomography (MDCT). Methods Consecutive patients with gastric glomus tumor which was confirmed by postoperative pathology from January 2004 to January 2012 in a tertiary hospital were included in the study. The MDCT images and medical records of the patients including the imaging features of the tumor on MDCT such as its location, number, shape, growth pattern, size, density and enhancement pattern were retrospectively reviewed. Results Altogether ten patients were included in the study, including seven women and three men, with a mean age of 46.6 years (range 25–67 years). Most patients had nonspecific clinical symptoms. All lesions were located at the gastric antrum, with a mean diameter of 2.7 cm. The gastric glomus tumor showed strong enhancement at the arterial phase, a progressive filled-in enhanced pattern and prolonged enhancement during multiphasic scans. Conclusions Gastric glomus tumor is clinically an extremely rare disease. The combination of tumor location, size and the characteristic enhancement pattern of the subepithelial lesion may suggest a diagnosis of gastric glomus tumor.

Objective To determine whether adding diffusion-weighted imaging (DWI) to gadoxetic acid-enhanced 3.0T magnetic resonance imaging (MRI) can improve the detection of hepatocellular carcinoma (HCC), particularly for small lesions (≤2 cm) in patients with liver cirrhosis. Methods Data of patients diagnosed with focal liver lesions who had undergone gadoxetic acid-enhanced 3.0T MRI and DWI were retrospectively reviewed. Two radiologists (the observers) reviewed independently MRI images in two reading sessions, that is, gadoxetic acid-enhanced images alone and the combination of DWI (b values: 0 and 600 s/mm2) and gadoxetic acid-enhanced images. They assigned to each lesion a confidence level based on a five-point scale. The area under the receiver operating characteristic curve (AUROC), sensitivity and positive predictive value (PPV) for the detection of HCC were calculated. Results Both observers found the AUROC of the gadoxetic acid-enhanced images was slightly higher than that of the combined DWI and gadoxetic acid-enhanced MRI images in the detection of HCC (observer 1: 0.947 ± 0.030 vs 0.896 ± 0.042, Z = 1.478, P = 0.139; observer 2: 0.917 ± 0.038 vs 0.868 ± 0.048, Z = 1.296, P = 0.195). The sensitivity for the gadoxetic acid set alone was slightly higher than that for the combined set for observer 1 (97% vs 84%) and slightly lower for observer 2 (74% vs 82%). The PPVs were slightly higher for the gadoxetic acid set alone than for the combined set for both observers (observer 1, 89% vs 80%; observer 2, 93% vs 78%); however, none of the differences were statistically significant (P > 0.05). Conclusion There is no benefit in adding DWI to gadoxetic acid-enhanced MRI for the detection of HCC at 3.0T.

Fabric, our second skin with moisture and thermal capacity for skin temperature regulation, can arouse feelings of pleasant and discomfort. To examine the neurocognitive ability and emotion of fabric tactile perception under different local temperatures, we used functional magnetic resonance imaging with the same denim fabric stimuli and forearm contact area, and found a functional dissociation: the affective regions was more involved during warm condition; the discriminative regions were more involved during neutral condition; the basis regions were significance during cool condition. The higher local skin temperature environment can result in the improvement of sensitivity and discriminability by dorsal pathway (spatial) and ventral pathway (frequency) for fabric perception. Our results help to explain how the brain uses internal models to interpret external fabric tactile stimuli with micro environmental change.

To compare the image quality (IQ) and radiation dose of high-pitch scan and prospective ECG-triggered sequence scan on a 128-slice DSCT system for patients with atrial fibrillation (AF). Pulmonary venous (PV) CTA was performed with two protocols, including high-pitch scan and prospective ECG-triggered sequence scan. For each protocol, 20 sex, age and body-mass-index (mean 24.2 kg/m(2)) matched patients were identified. Two experienced radiologists, who were blinded to the scan protocols, independently graded the CT images of the two groups by a 5-point scale for subjective IQ assessment. Measured CT attenuation (Hounsfield units ± standard deviation), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at various anatomic locations were also recorded for objective IQ evaluation. Radiation exposure parameters [dose length product (DLP) and effective radiation dose (ERD)] were compared. Twenty-three patients (57.5 %) showed an ECG pattern of AF in total. Subjective IQ was rated excellent in 100 % for the high-pitch scan group, while minor step artifacts were observed in two patients (10 %) with arrhythmia for the prospective ECG-triggered sequence group. There was no significant difference on IQ, neither by subjective, nor by objective measures (SNR, CNR) between the two groups. The ERD of high-pitch flash scan and prospective ECG-triggered sequence scan were 0.9 (± 0.25) and 2.9 (± 0.69) mSv, respectively. Significantly lower radiation was achieved by using high-pitch flash scan (P < 0.05). High-pitch flash scan can provide similar subjective and objective IQ compared with prospective ECG-triggered sequence scan for PV CTA, while radiation exposure was significantly reduced.

OBJECTIVE To evaluate the performance of sinogram-affirmed iterative (SAFIRE) reconstruction on image quality of low-dose lung computed tomographic (CT) screening compared with filtered back projection (FBP). METHODS Three hundred four patients for annual low-dose lung CT screening were examined by a dual-source CT system at 120 kilovolt (peak) with reference tube current of 40 mA·s. Six image serials were reconstructed, including one data set of FBP and 5 data sets of SAFIRE with different reconstruction strengths from 1 to 5. Image noise was recorded; and subjective scores of image noise, images artifacts, and the overall image quality were also assessed by 2 radiologists. RESULTS The mean ± SD weight for all patients was 66.3 ± 12.8 kg, and the body mass index was 23.4 ± 3.2. The mean ± SD dose-length product was 95.2 ± 30.6 mGy cm, and the mean ± SD effective dose was 1.6 ± 0.5 mSv. The observation agreements for image noise grade, artifact grade, and the overall image quality were 0.785, 0.595 and 0.512, respectively. Among the overall 6 data sets, both the measured mean objective image noise and the subjective image noise of FBP was the highest, and the image noise decreased with the increasing of SAFIRE reconstruction strength. The data sets of S3 obtained the best image quality scores. CONCLUSION Sinogram-affirmed iterative reconstruction can significantly improve image quality of low-dose lung CT screening compared with FBP, and SAFIRE with reconstruction strength 3 was a pertinent choice for low-dose lung CT.

Lung cancer is among the most common causes of cancer-related mortality. It has a high mortality rate and resistance to chemotherapy due to its high metastatic potential. Naringenin, a bioactive compound identified in several fruits, displays anti-inflammatory and antitumor effects. Furthermore, naringenin mitigates the migration of several human cancer cell types. However, the effects of naringenin on lung cancer remain unclear. The current study investigated the mechanisms of naringenin on the migration of lung cancer A549 cells. The results indicate that significant alteration in A549 cell proliferation was observed in response to naringenin (0-300 µM) treatment for 24 and 48 h. Furthermore, a dose-dependent migration inhibition of A549 in the presence of naringenin was observed by healing and transwell migration assays. In addition, a zymography assay revealed that naringenin exhibited a concentration-dependent inhibition of matrix metalloproteinase (MMP)-2 and -9 activities. Furthermore, naringenin also inhibited the activities of AKT in a dose-dependent manner. These observations indicated that naringenin inhibited the migration of lung cancer A549 cells through several mechanisms, including the inhibition of AKT activities and reduction of MMP-2 and -9 activities.

Objectives The purpose of this study was to assess the differences in sonographic features of papillary thyroid carcinoma between neck lymph node metastatic and non-metastatic groups. Methods A total of 155 patients with 155 papillary thyroid carcinoma nodules were included and divided into two groups: with neck lymph node metastases (52 cases) and without neck lymph node metastases (103 cases). The size, shape, border, margin, halo, internal architecture, echogenicity, echo homogeneity, calcifications, and contact extent between the nodule border and thyroid capsule were evaluated by gray scale sonography, and color Doppler sonography was applied to assess the vascularization distribution and vascularization degree in the nodules. The peak systolic velocity, pulsatility index, resistive index, peak systolic velocity difference, pulsatility index difference, and resistive index difference were measured by pulsed Doppler sonography in 80 lesions. The differences in the sonographic features of papillary thyroid carcinoma between the metastatic and nonmetastatic groups were investigated. Results The differences in the size, percentage of the nodule border that contacted the thyroid capsule, calcifications, vascularization degree, and resistive index difference of the lesions were statistically significant between the metastatic and nonmetastatic groups (P Conclusions Our findings suggest that a larger size, a greater contact percentage, combined microcalcifications and macrocalcifications, a higher blood supply, and a higher resistive index difference were significantly more common in the metastatic group compared to the nonmetastatic group.

Pulmonary enteric adenocarcinoma is a markedly rare pathological type of lung adenocarcinoma. As the pancreas is a relatively uncommon site for metastasis, the present case is even more unusual. A 62-year-old male was admitted to hospital following the identification of masses in the left chest wall, right abdominal wall and right upper limb, but with no respiratory symptoms. Computed tomography (CT) of the chest revealed a lump in the lung and a mass in the left chest wall, and 18F-fluorodeoxyglucose (18F-FDG) uptake by the lumps was increased. An enhanced abdominal CT revealed a hypodense and homogeneous mass on the head of the pancreas, which was slightly enhanced compared with normal pancreatic tissue. In addition, the 18F-FDG uptake of the lesion was increased and the standardized uptake value (SUV) delayed was not evidently decreased compared with SUVearly. A number of other abnormal metabolic lesions were also identified using positron emission tomography/CT, whereas no abnormal 18F-FDG uptake was identified in the gastrointestinal organ. Furthermore, rectocolonoscopy was performed to exclude diagnosis of metastatic colorectal adenocarcinoma. The hematoxylin- and eosin-stained smears of the masses in the right lung and left chest demonstrated an enteric pattern, which shared morphological and immunohistochemical (IHC) features with those of colorectal adenocarcinoma. The IHC detection revealed that the lesions in the right lung were positive for cytokeratin 7 (CK7), and negative for CK20 and thyroid transcription factor 1 (TTF-1), and the expression of caudal type homeobox 2 (CDX2) was weakly positive; the masses in the left chest wall were positive for CK7, negative for TTF-1, and CK20 and CDX2 were weakly expressed.

Lumbrokinase, a novel antithrombotic agent, purified from the earthworm Lumbricus rubellus, has been clinically used to treat stroke and cardiovascular diseases. However, inflammatory responses associated with the cardioprotective effect of lumbrokinase remain unknown. In this study, the signaling pathways involved in lumbrokinase-inhibited expressions of inflammation mediators were investigated in rats subjected to myocardial ischemia-reperfusion (I-R) injury. The left main coronary artery of anesthetized rats was subjected to 1h occlusion and 3h reperfusion. The animals were treated with/without lumbrokinase and the severities of I-R-induced arrhythmias and infarction were compared. Lumbrokinase inhibited I-R-induced arrhythmias and reduced mortality, as well as decreased the lactate dehydrogenase levels in carotid blood. Lumbrokinase also inhibited the enhancement of I-R induced expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and matrix metalloproteinase (MMP)-9 through toll-like receptor 4 (TLR4) signaling pathway. Moreover, our results demonstrated that stimulation with lumbrokinase decreases the phosphorylation of JNK, IκB, and NF-κB. These findings suggested that lumbrokinase is a potent cardioprotective drug in rats with I-R injury. The cardioprotective effects of lumbrokinase may be correlated with its inhibitory effect on the I-R-induced expressions of COX-2, iNOS and MMP-9, mediated by TLR4 signaling through JNK and NF-κB pathways.

Purpose The aim of this study was to assess the technical feasibility, efficacy, and complications of CT-guided interstitial brachytherapy for treating inoperable non-small cell lung cancer (NSCLC). Materials and methods Twenty one patients were included in this prospective study. The median age was 72.6 years (57–85). Tumors were treated with brachytherapy that was positioned under CT-fluoroscopy. The treatment planning system (TPS) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution. The median matched peripheral dose (MPD) was 130Gy (range, 100–160Gy). All procedures were performed under local anesthesia. A follow-up CT was performed 6 weeks later and every 3 months post implantation. Results Follow-up period was 2–30 months. The mean diameter of the 21 lung tumors was 4.6cm (range, 2.8–6.5cm). The response rate of pain relief was 83.3% (10/12). The pain-free duration was 0–12 months (median: 6 months; 95% CI: 3–9 months). Overall responding rate (CR+PR) for this group of patients was 71.4%. Local tumor control rate was 85.7%. Six (28.6%) patients died as a result of primary tumor progression; thirteen (61.9%) patients died of multi-organ failure or other metastases. Two (9.5%) patients survived to follow-up. At the time of analysis, the median survival time for all patients was 10 months (95% CI: 6.6–13.4 months), with 1 year and 2 year survival rates were 42.4% and 6.5%, respectively. Median survival time for stage II, stage III, and stage IV was 20 months, 9 months, and 8 months, respectively. No major complications were observed. Minor complications (19%) included mild pneumothorax ( n =1), hemosputum ( n =1), pleural effusion ( n =1), and localized skin erythema ( n =1). None of these complications required further treatment, although hospital discharge was delayed. No 125 I seeds migrated to other tissues or organs. Conclusion Minimally invasive CT-guided interstitial brachytherapy is safe, useful, less complicated and considered as a palliative treatment option for inoperable non-small cell lung cancer.

OBJECTIVE The purpose of this study was to select the optimal monochromatic level for gemstone spectral imaging (GSI) to minimize both the image noise and beam-hardening artifacts (BHAs) in nonenhanced cranial computed tomography (CT). MATERIALS AND METHODS One hundred subjects scanned with GSI mode on Discovery CT750HD were enrolled. Six sets of CT images were obtained from a single GSI acquisition: conventional 140 kilovolt (peak) (kV[p]) polychromatic images and 5 sets of monochromatic images (80, 75, 70, 65, and 60 kiloelectron volts [keV]). The background noise in the corona and the BHA in 4 different anatomic regions (medulla oblongata, cerebellar, pons, and the inferior part of frontal lobes) were measured and compared between the polychromatic and monochromatic images. Beam-hardening artifact is defined as the square root of the squared noise difference between the region of interest and background. RESULTS The background noise with the monochromatic sets reduced by -36%, -11%, 11%, 10%, and -14%, respectively, compared to the polychromatic image. For BHA, the reductions were 73%, 91%, 92%, and 80%; 53%, 75%, 65%, and 41.%; 27%, 59%, 44%, and 26%; 7%, 46%, 25%, and 20%; and -14%, 33%, 6%, and 19% for the 4 regions of interest. Both the 70 and 65 keV sets had positive background noise reduction (P = 0.285) and BHA reduction with 70 keV were statistically higher (P < 0.05). CONCLUSION In the nonenhanced cranial CT with GSI, the optimal monochromatic level was determined at 70 keV to provide both image noise reduction (11%) and BHA reduction compared to the conventional polychromatic images.

BACKGROUND Intracranial large artery disease (ICLAD), such as stenosis and calcification, is common in Chinese patients with stroke. However, little is known about ICLAD and its association with large arterial stiffness in hypertensive patients. METHODS We recruited 270 (mean age 61.0 years, 45.6% male) untreated hypertensive patients without stroke from a community in Shanghai, China. ICLAD was detected by computerized tomographic angiography (CTA). Carotid-femoral pulse wave velocity (cf-PWV), office, and 24-h ambulatory pulse pressure (PP) as well as ambulatory arterial stiffness index (AASI) were determined as the measures of arterial stiffness. RESULTS Among all participants, 26 (9.6%) had concurrent intracranial arterial stenosis and calcification, 11 (4.1%) stenosis only, and 71 (26.3%) calcifications only. After adjustment for age, mean arterial pressure, and other covariables, there was significant difference in cf-PWV (13.1 vs. 13.7 vs. 15.0 m/s; P = 0.0015) and 24-h PP (46.7 vs. 48.8 vs. 55.7 mm Hg; P = 0.0007) between patients with normal vessels (n = 162), with stenosis or calcification (n = 82), and with both lesions (n = 26). Multiple ordinal logistic regression analyses showed that both cf-PWV and 24-h PP were independently associated with ICLAD. Odds ratios (95% confidence interval (CI)) of ICLAD after multivariable and mutually adjustment were 1.51 (1.09-2.10) and 1.46 (1.06-2.01) for 1-s.d. increase in cf-PWV and 24-h PP, respectively. No significant association (P ≥ 0.10) with AASI or office PP was observed in multivariable analysis. CONCLUSION Increased arterial stiffness was independently associated with ICLAD. cf-PWV and 24-h PP might be useful in identifying those more likely to have ICLAD among hypertensive patients.

Background/Aims: To investigate if and where abnormal iron accumulation in white matter fibers occurs in patients with Alzheimer’s disease (AD) by phase imaging and to relate these findings to white matter tract degeneration assessed by diffusion tensor imaging. Methods: Twenty-five patients with AD and 20 normal controls underwent phase imaging and diffusion tensor imaging with a 3.0-tesla system. White matter fibers including fornix (Fx), genu of corpus callosum (GCC), splenium of corpus callosum (SCC), bilateral posterior cingulum (PC), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and frontal occipital fasciculus (IOF) were measured on a fractional anisotropy (FA) map, mean diffusivity (MD) map and phase map. Results: Significantly decreased phase values and FA values in the Fx and PC regions were found in the AD group. The phase value in Fx had a moderately positive correlation with the FA value (r = 0.666, p = 0.000) in the AD group. Meanwhile, phase values in PC showed positive correlation with FA values (right side: r = 0.436, p = 0.033; left side: r = 0.458, p = 0.022, respectively). Conclusion: Iron accumulation of Fx and PC regions was significantly positively correlated with FA value, indicating that abnormal iron deposition may be one of the causes of white matter disruption in AD.

In this study, partially hydrolyzed ethylene vinyl acetate (EVA) copolymers with three hydrolysis degrees (12.2%, 32.6% and 46.9%) were obtained by alkaline hydrolysis of EVA copolymer, characterized by Fourier-transform infrared spectroscopy (FTIR), (1)H NMR and gel permeation chromatography (GPC). Paclitaxel-loaded and drug-free films based on the partially hydrolyzed EVA copolymers were fabricated. The swelling behaviors, crystallinities, mechanical properties of the fabricated films were investigated, and the effects of hydrolysis degree, film thickness and drug loading dose on in vitro drug release from the films were also investigated. In vitro swelling study showed that the swelling of partially hydrolyzed EVA films was greater than the EVA film and the film with higher hydrolysis degree swelled more intensively. X-ray diffraction (XRD) results exhibited that the crystallinity of the polymer increased with increasing hydrolysis degree. In paclitaxel-loaded EVA film, a part of paclitaxel was in crystalline form; while in paclitaxel-loaded partially hydrolyzed EVA films, paclitaxel was distributed in amorphous form or molecularly dispersed. In the in vitro drug release test, the film with higher hydrolysis degree and smaller thickness released paclitaxel more quickly. With higher drug loading dose, the drug release rate was larger. The partially hydrolyzed EVA films were applied for drug delivery systems for the first time, and demonstrated to have great capability of controlling drug release thanks to the adjustable hydrolysis degree.

To evaluate the clinical value of a body mass index (BMI) based tube current (mA) selection method for obtaining consistent image quality with dose optimization in MDCT prospective ECG gated coronary calcium scoring. A formula for selecting mA to achieve desired image quality based on patient BMI was established using a control group (A) of 200 MDCT cardiac patients with a standard scan protocol. One hundred patients in Group B were scanned with this BMI-dependent mA for achieving a desired noise level of 18 HU at 2.5 mm slice thickness. The CTDIvol and image noise on the ascending aorta for the two groups were recorded. Two experienced radiologists quantitatively evaluated the image quality using scores of 1-4 with 4 being the highest. The image quality scores had no statistical difference (P = 0.71) at 3.89 ± 0.32, 3.87 ± 0.34, respectively, for groups A and B of similar BMI. The image noise in Group A had linear relationship with BMI. The image noise in Group B using BMI-dependent mA was independent of BMI with average value of 17.9 HU and smaller deviations for the noise values than in Group A (2.0 vs. 2.9 HU). There was a 35% dose reduction with BMI-dependent mA selection method on average with the lowest effective dose being only 0.35 mSv for patient with BMI of 18.3. A quantitative BMI-based mA selection method in MDCT prospective ECG gated coronary calcium scoring has been proposed to obtain a desired and consistent image quality and provide dose optimization across patient population.

Angiostrongylus cantonensis causes eosinophilic meningitis or meningoencephalitis, yet little is known about demyelination caused by this parasite. To define the course of demyelination caused by A. cantonensis, we analyzed the expression of myelin proteins including myelin-associated glycoprotein (MAG), myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), and proteolipid protein (PLP) in brain and cerebrospinal fluid (CSF)-like fluid of infected and uninfected BALB/c mice. In A. cantonensis-infected mice, the expression of MAG, MBP, MOBP, and PLP mRNAs in brain tissue was decreased, while expression of the corresponding proteins was significantly increased in CSF-like fluid. Light microscopy revealed perivascular infiltrates in the brain during meningoencephalitis, suggesting that the cause of demyelination in angiostrongyliasis was immune system attack on the oligodendrocytic myelin sheath and subsequent release of myelin proteins into the CSF. Thus, intracerebral myelin breakdown in angiostrongyliasis may be a response to inflammatory mediators and the cause of increased myelin proteins in the CSF-like fluid.

Many patients with malignant gastroduodenal obstruction have an unresectable primary lesion and distant metastases, which may prompt palliative management to allow the patient to eat and to improve the quality of life. Intraluminal metallic stent implantation (MSI) under fluoroscopic guidance has been reported to be an effective option for symptomatic relief in these patients, with a good safety record. An alternative, dual interventional therapy (DIT), has been used during the last decade, in which prosthesis insertion is followed by intra-arterial chemotherapy via the tumor-feeding arteries. The aim of this study was to compare success rates, complication rates, and survival time between MSI and DIT in patients who presented with gastroduodenal obstruction from advanced upper gastrointestinal tract cancer. All consecutive patients with malignant gastroduodenal obstruction seen at our center between October 2002 and August 2007 were retrospectively studied. Patients were treated palliatively by either MSI or DIT by the patient’s or the next of kin’s decision. Outcomes included technical and clinical success, complication rates, and survival. Of the 164 patients with malignant gastric and duodenal outlet obstructions, 80 (49%) underwent stent insertion as the primary therapy, while the remaining 84 (51%) received DIT. Clinical characteristics were similar between the two groups. In the MSI cohort initial stent implantation was successful in 73 patients (91%), two stents were used in 5 patients, and delayed additional stent insertion for stent obstruction related to tumor overgrowth was required in 3 patients during follow-up. In the DIT cohort the technical success rate was 94%, 3 patients required two stents, and stent obstruction occurred in 2 patients after initial stent placement. Early postprocedural clinical success, indicated by average dysphagia score, improved significantly in both groups: MSI group, from 4.56 to 1.51 (P < 0.01); and DIT group, from 4.38 to 1.48 (p < 0.01). There were no short-term complications. Late complications including hematemesis (n = 3), migration (n = 12), and stent occlusion due to tumor overgrowth (n = 5) were evenly distributed between the groups. In the DIT group chemotherapy-induced neutropenia and transient renal dysfunction were detected in six patients, which improved after symptomatic management. Mean survival time after the procedure was 5.9 and 11.1 months for MSI and DIT, respectively (P < 0.001). In conclusion, both MSI and DIT offer effective palliation for malignant gastroduodenal obstruction, but DIT appears to offer superior survival over MSI alone. Ideally, a prospective randomized trial comparing these two techniques should be carried out to validate this result.

To assess the clinical feasibility of diagnosing and staging liver fibrosis by apparent diffusion coefficient (ADC).Totally, 43 patients (mean age 29.3 years) with chronic hepatitis by liver biopsy and 7 healthy controls (mean age 39.9 years) underwent liver diffusion weighted imaging (DWI) with four b values: 0, 200, 500, and 1000 s/mm2 respectively. The liver fibrosis was staged according to Ishak fibrosis stage. The ADC value of liver fibrosis patients and healthy controls was compared. The correlation of ADC value and liver fibrosis staging was analyzed.The histological staging showed 8 stage 1 patients, 10 stage 2 patients, 6 stage 3 patients, 9 stage 4 patients, 8 stage 5 patients and 2 stage 6 patients. The mean ADC value of liver fibrosis patients was significantly lower than that of healthy controls except for stage 1 group (P0.05). There was a negative correlation between liver fibrosis staging and ADC value (r = -0.697 with b=500 s/mm2, P0.01). Receiver operating characteristic (ROC) curve of ADC value of advanced liver fibrosis (Ishak stage F3 and higher) showed that area under curve = 0.913, 0.825, and 0.794 with b = 500, 1000, and 200 s/mm2, respectively (95% confidence interval: 83.6%-99.0%, 70.7%-94.3%, 66.5%-92.4%; P0.05). When b value was 500 s/mm2, the sensitivity (84%) and specificity (80%) of DWI for diagnosis of advanced liver fibrosis were the highest.DWI is proved to be a useful clinical tool in the quantitative evaluation of liver fibrosis and in the prediction of the process of liver fibrosis with the recommendable b value (500 s/mm2).

Objective To investigate the feasibility of whole body diffusion weighted imaging (WB-DWI) in screening metastasis. Methods WB-DWI was performed in 24 patients diagnosed with various types of primary tumors. The three-dimensional maximum intensity projection reconstruction and black-and-white flip technique were used to observe metastatic lesions, and the results were compared with those of bone scintigraphy. Results By WB-DWI scanning sequence at b = 800 s/mm2, all the bone lesions found by bone scintigraphy in the cohort were well identified, and other lesions of soft tissue and organs were also well demonstrated. Its screening capability was equivalent with bone scintigraphy in screening metastases in bones (P = 0.062). Conclusion WB-DWI was practicable with the parameter settings attempted in metastases screening.