The Value of Amide Proton Transfer MRI in the Diagnosis of Malignant and Benign Urinary Bladder Lesions: Comparison With Diffusion-Weighted Imaging.

BACKGROUND: Conventional magnetic resonance imaging (MRI) has certain limitations in distinguishing between malignant and benign urinary bladder (UB) lesions. Amide proton transfer (APT) imaging may provide more diagnostic information than diffusion-weighted imaging (DWI) to distinguish between malignant and benign UB. PURPOSE: To investigate the potential of APT imaging in the diagnosis of malignant and benign UB lesions and to compare its diagnostic efficacy with that of conventional DWI. STUDY TYPE: Prospective. SUBJECTS: Eighty patients with UB lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T/turbo spin echo (TSE) T1-weighted and T2-weighted imaging, single-shot echo planar DWI, and three-dimensional TSE APT imaging. ASSESSMENT: Patients underwent radical cystectomy or transurethral resection of the bladder lesions within 2 weeks after CT urography and MRI examination. APT signal intensity in UB lesions was quantified by the asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) values were measured and compared between malignant and benign UB lesions. STATISTICAL TESTS: Kolmogorov-Smirnov test, Student's t test or Mann-Whitney U test, Spearman rank correlation coefficient, area under the receiver operating characteristic (ROC) curve (AUC), Delong test, and intraclass correlation coefficient (ICC). The significance threshold was set at P < 0.05. RESULTS: Thirty-two patients had pathologically confirmed benign UB lesions, including 2 bladder leiomyomas, 1 submucosal amyloidosis, 1 inflammatory myofibroblastic tumor, and 28 inflammatory lesions, and 48 patients had pathologically confirmed urothelial carcinoma. Urothelial carcinomas showed significantly higher MTRasym values (1.53% [0.74%] vs. 0.85% [0.23%]) and significantly lower ADC values (1.24 ± 0.34 × 10-3 mm2/s vs. 1.43 ± 0.22 × 10-3 mm2/s) than benign UB lesions. The MTRasym value (AUC = 0.928) was significantly better in differentiating urothelial carcinoma from benign UB lesions than the ADC value (AUC = 0.722). DATA CONCLUSION: APT imaging may have value in discriminating malignant from benign UB lesions and has better diagnostic performance than DWI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Prognostic Value of Pre-Autologous Stem Cell Transplantation PET/CT in Diffuse Large B-Cell Lymphoma: The Deauville Score Is Prognostically Superior to ΔSUVmax.

OBJECTIVE: The predictive value of pre-autologous stem cell transplantation (pre-ASCT) positron emission tomography/computed tomography (PET/CT) scans according to different criteria remains elusive in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 46 DLBCL patients treated with pre-ASCT were enrolled in the present study, and two methods, Deauville score and maximal standardized uptake value reduction (ΔSUVmax), were used to evaluate the PET/CT scans before transplantation. RESULTS: In patients with Deauville 1-3 and ≥4, the 2-year progression-free survival (PFS) rates were 82.8 and 11.8% (p < 0.001), respectively, while the 2-year overall survival (OS) rates were 89.7 and 41.2%, respectively (p < 0.001). When using the ΔSUVmax cut-off of 66% criterion, in patients with a ΔSUVmax of >66 and ≤66%, the 2-year PFS rates were 78.1 and 7.1%, respectively (p < 0.001), while the 2-year OS rates were 87.5 and 35.7%, respectively (p < 0.001). In the univariate analysis, the ΔSUVmax, Deauville score, NCCN-IPI and serum lactate dehydrogenase levels were significantly correlated with the 2-year PFS/OS. Furthermore, the multivariate analysis revealed that the Deauville score was an independent prognostic factor for 2-year PFS. CONCLUSION: The present results indicate that PET/CT scans at pre-ASCT can predict the survival of DLBCL patients, and the Deauville score is better than ΔSUVmax in prognostic prediction.

Comparative analysis of amide proton transfer and diffusion-weighted imaging for assessing Ki-67, p53 and PD-L1 expression in bladder cancer.

RATIONALE AND OBJECTIVES: To evaluate amide proton transfer (APT) imaging for assessing Ki-67, p53 and PD-L1 status in bladder cancer (BC) and compare its diagnostic efficacy with that of diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Consecutive patients suspected of BC were recruited for preoperative multiparametric MRI. APT signal was quantified by asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) were measured by two radiologists, with interobserver agreement assessed. Spearman's correlation analyzed MTRasym values and molecular markers. The Whitney U test evaluated MTRasym and ADC variation based on molecular marker status. Optimal cutoff points were determined using area under the curve (AUC) analysis. RESULTS: 88 patients (72 ± 10 years; 77 men) with BC were studied. MTRasym values were significantly correlated with Ki-67, p53 and PD-L1 levels (P < 0.05). Higher MTRasym values were found in high Ki-67 expression BCs (1.89% [0.73%] vs. 1.23% ± 0.26%; P < 0.001), high p53 expression BCs (1.63% [0.56%] vs. 1.24% [0.56%]; P < 0.001) and positive PD-L1 expression BCs (2.02% [0.81%] vs. 1.48% [0.38%]; P < 0.001). Lower ADCs were found in high Ki-67 expression BCs (1.06 ×10-3 mm2/s [0.32 ×10-3 mm2/s] vs. 1.38 ×10-3 mm2/s [0.39 ×10-3 mm2/s]; P < 0.001). For p53 status, an MTRasym threshold of 1.27% had 95% sensitivity, 60% specificity, and AUC of 0.781. For PD-L1 status, a 1.90% threshold had 88% sensitivity, 92% specificity, and AUC of 0.859. CONCLUSION: APT may significantly enhance the preoperative assessment of BC aggressiveness and inform targeted immunotherapy decisions, with performance superior to DWI.

Radiomics of Preoperative Multi-Sequence Magnetic Resonance Imaging Can Improve the Predictive Performance of Microvascular Invasion in Hepatocellular Carcinoma.

Background: The aim of the study is to demonstrate that radiomics of preoperative multi-sequence magnetic resonance imaging (MRI) can indeed improve the predictive performance of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 206 patients with pathologically confirmed HCC who underwent preoperative enhanced MRI were retrospectively recruited. Univariate and multivariate logistic regression analysis identified the independent clinicoradiologic predictors of MVI present and constituted the clinicoradiologic model. Recursive feature elimination (RFE) was applied to select radiomics features (extracted from six sequence images) and constructed the radiomics model. Clinicoradiologic model plus radiomics model formed the clinicoradiomics model. Five-fold cross-validation was used to validate the three models. Discrimination, calibration, and clinical utility were used to evaluate the performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the prediction accuracy between models. Results: The clinicoradiologic model contained alpha-fetoprotein (AFP)_lg10, radiological capsule enhancement, enhancement pattern and arterial peritumoral enhancement, which were independent risk factors of MVI. There were 18 radiomics features related to MVI constructed the radiomics model. The mean area under the receiver operating curve (AUC) of clinicoradiologic, radiomics and clinicoradiomics model were 0.849, 0.925 and 0.950 in the training cohort and 0.846, 0.907 and 0.933 in the validation cohort, respectively. The three models' calibration curves fitted well, and decision curve analysis (DCA) confirmed the clinical usefulness. Compared with the clinicoradiologic model, the NRI of radiomics and clinicoradiomics model increased significantly by 0.575 and 0.825, respectively, and the IDI increased significantly by 0.280 and 0.398, respectively. Conclusions: Radiomics of preoperative multi-sequence MRI can improve the predictive performance of MVI in HCC.

[Values of ocular hemodynamics and serum endothelin-1 in the early diagnosis of diabetic retinopathy].

OBJECTIVE: To evaluate the values of ocular hemodynamics and serum endothelin-1 (ET-1) in the early diagnosis of diabetic retinopathy (DRP). METHODS: A total of 85 DRP patients were examined by ophthalmoscope and fluorescein angiography and divided into 3 groups: no obvious retinopathy (n = 20), non-proliferative diabetic retinopathy (n = 35) and proliferative diabetic retinopathy (n = 30). Control group included 15 healthy volunteers. The peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of ophthalmic artery (OA) and central retinal artery (CRA) were measured by color Doppler energy imaging. The level of endothelin-1 was measured by radioimmunoassay. Then plasma ET-1 levels and eye vascular hemodynamic parameters were compared with correlation and diagnostic specificity after data analysis. RESULTS: Compared with the control group, DRP, EDV and PSV decreased progressively while RI increased gradually (P < 0.05). EDV and RI were more sensitive than PSV in diagnosis. The plasma level of ET-1 was significantly higher than that of control group (P < 0.05). And it was correlated positively with RI and negatively with PSV and EDV of CRA. The diagnostic value of EDV was higher than that of ET-1 level. CONCLUSION: Ocular hemodynamics become abnormal during the early stage of DRP and worsen with the progress of DRP. An elevated plasma level of ET-1 may lead to the abnormal of retinal hemodynamics. The test of plasma ET-1 and the examination of ocular hemodynamics may play an important role in the early diagnosis of DRP.

[Effects of neural stem cells transplanted into an animal model of Alzheimer disease on Aß plaques].

OBJECTIVE: To explore the effects on Aß plaques of neural stem cells transplanted into an Alzheimer disease mouse model. METHODS: A total of twenty 12-months-old APP+PS1 double transgenic AD mice were randomly divided into two groups.One group received neural stem cells transplantation, that was NSC group, another mice received an equal quantity 0.01 mol/L PBS, as positive control group. After 5 weeks transplantation, the total number of Aß plaques examined by immunohistochemistry, the ratio of compact of Aß plaques by TS staining, and whether NSCs migrate into Aß plaques by immunofluorescence monitoring. RESULTS: There was no difference in total number of Aß plaques between NSC group (181 ± 12) and PBS (179 ± 14) group after transplantation (P > 0.05). There was no difference in the number of TS+ plaques between NSC group (54.9%) and PBS (55.7%) group after eight weeks NSCs transplantation (P > 0.05). (2) However, engrafted NSCs showed partial chemotaxis toward Aß plaques. CONCLUSION: NSCs transplantation did not have a significant impact on Aß plaques of AD mice, but the tropism of engrafted NSCs may be capable of replacing lost or damaged cells and reverse the course of AD mice in some extent.

[In vivo labeling of rat neural progenitor cells in subventricular zone with superparamagnetic iron oxide for tracking of magnetic resonance imaging].

OBJECTIVE: To explore the feasibility of in vivo labeling of adult rat neural progenitor cells (NPCs) in subventricular zone (SVZ) with superparamagnetic iron oxide particles (SPIOs) for tracking of magnetic resonance imaging (MRI). METHODS: A total of 7 SD rats were stereotactically injected with 3 µl SPIOs (7 mg Fe/ml) into anterior horn of right lateral ventricle and then 5-bromo-2'-deoxyuridine (BrdU) was injected intraperitoneally once daily for 1 week. MRI was performed at 1, 3, 7 and 14 days post-injection. After the final MRI scan, all rats were transcardially perfused and their brains removed and fixed. The sections were processed for Prussian blue iron staining and Prussian blue plus BrdU immunohistochemical staining. RESULTS: In all experimental animals, SPIOs were predominantly located in the anterior horn of right lateral ventricle and partial SPIOs entered the ventricular system. A needle path and a distribution of SPIOs along rostral migratory stream (RMS) towards olfactory bulb (OB) were depicted at the sagittal view of T2(*)WI, moderate MR artifact was visible and SPIOs tracking NPCs were successful (success rate of 100%). The result of staining showed SPIOs labeling NPCs were effective. And the labeling rates were 75.5%, 42.3%, 23.6% in SVZ, RMS and OB respectively. CONCLUSION: Effective in vivo labeling of adult rat NPCs in SVZ with SPIOs is feasible. And dynamical migration of labeling NPCs along RMS towards OB may be visualized on MRI.

Evaluation of amide proton transfer imaging for bladder cancer histopathologic features: A comparative study with diffusion- weighted imaging.

PURPOSE: To assess the ability of amide proton transfer (APT) imaging, in comparison with diffusion-weighted imaging (DWI), to differentiate low-grade from high-grade bladder tumors and predict the aggressiveness of bladder cancer (BCa). METHODS: Forty-eight patients diagnosed with BCa confirmed by histopathological findings who underwent magnetic resonance (MR) imaging, including APT imaging and DWI (b = 0, 1000 sec/mm2), were enrolled in this study. The asymmetric magnetization transfer ratio (MTRasym) was defined as the magnetization transfer asymmetry at 3.5 ppm. MTRasym and apparent diffusion coefficients (ADCs) were compared between the low- and high-grade groups and between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) in terms of the areas under the receiver operating characteristic curves (AUCs). RESULTS: The MTRasym values were significantly higher in patients with high-grade bladder tumors than in those with low-grade tumors (1.61 % [0.76 %], 1.12 ± 0.3 %; P = 0.000) and in MIBC than in NMIBC (2.53 ± 0.67 %, 1.38 % [0.35 %]; P = 0.000). The AUCs of MTRasym were significantly larger than those of ADC for differentiating MIBC from NMIBC (0.973, 0.771; P = 0.016). Adding APT imaging to DWI significantly improved the diagnostic accuracy for differentiating MIBC from NMIBC versus DWI alone (0.985, 0.876; P = 0.013). CONCLUSIONS: APT imaging can predict tumor grade and aggressiveness in BCa. The diagnostic performance of APT imaging in predicting tumor aggressiveness was better than that of DWI, and adding APT imaging to DWI significantly improved the diagnostic accuracy of predicting tumor aggressiveness versus DWI alone.

Morphological and biomechanical remodeling of the hepatic portal vein in a swine model of portal hypertension.

OBJECTIVES: To obtain the morphological and biomechanical remodeling of portal veins in swine with portal hypertension (PHT), so as to provide some mechanical references and theoretical basis for clinical practice about PHT. METHODS: Twenty white pigs were used in this study, 14 of them were subjected to both carbon tetrachloride- and pentobarbital-containing diet to induce experimental liver cirrhosis and PHT, and the remaining animals served as the normal controls. The morphological remodeling of portal veins was observed. Endothelial nitric oxide synthase expression profile in the vessel wall was assessed at both mRNA and protein level. The biomechanical changes of the hepatic portal veins were evaluated through assessing the following indicators: the incremental elastic modulus, pressure-strain elastic modulus, volume elastic modulus, and the incremental compliance. RESULTS: The swine PHT model was successfully established. The percentages for the microstructural components and the histological data significantly changed in the experimental group. Endothelial nitric oxide synthase expression was significantly downregulated in the portal veins of the experimental group. Three incremental elastic moduli (the incremental elastic modulus, pressure-strain elastic modulus, and volume elastic modulus) of the portal veins from PHT animals were significantly larger than those of the controls (P < 0.05), whereas the incremental compliance of hepatic portal vein decreased. CONCLUSIONS: Our study suggests that the morphological and biomechanical properties of swine hepatic portal veins change significantly during the PHT process, which may play a critical role in the development of PHT and serve as potential therapeutic targets during clinical practice.

[Effects of RNA interference targeting P2X7 receptor on microglial phagocytosis of amyloid-ß protein].

OBJECTIVE: To investigate the effect of silencing P2X7 receptor (P2X7R) by RNA interference on microglial phagocytosis of amyloid-ß (Aß) protein and to explore its possible mechanism. METHODS: The small interfering RNA (siRNA) targeting the P2X7R gene was identified. The microglial cells activated by Aß1-42 were infected with the Lipofectamine-siP2X7R and it was designated as siP2X7R group. Microglia infected with Lipofectamine-siNC was designated as siNC group and non-infected cells as con group. The levels of P2X7R mRNA were detected by real-time PCR and the P2X7R protein was determined by Western blotting. The levels of IL-1ß and TNF-α were measured by ELISA. The microglial phagocytosis of Aß1-42 was observed by ELISA and immunocytochemistry staining. RESULTS: Detected by the Real-time PCR, the expression level of P2X7R mRNA of siP2X7R group decreased significantly versus siNC and con groups (P<0.05). The lowered expression of P2X7R protein detected by Western blotting was consistent with Real-time PCR. After RNA interference silencing P2X7R, the levels of IL-1ß and TNF-α detected by ELISA in siP2X7R group less than those in con, siNC groups, significantly (P<0.05). In con, siNC and siP2X7R groups respectively, the levels of Aß1-42 in supernatant were (423±20) pg/ml, (417±16) pg/ml, (296±30) pg/ml and the levels of Aß1-42 in the microglia were (190±37) pg/ml, (187±39) pg/ml, (322±26) pg/ml. Compared to siNC and con groups, in siP2X7R group the levels of Aß1-42 in supernatant decreased (P<0.05) and the levels of Aß1-42 in the microglia increased (P<0.05). Aß1-42 immunofluorescence staining showed that the red fluorescent products were seen in the cytoplasm of most microglias in siP2X7R group, but in con or siNC groups in only few microglias these products were depicted. CONCLUSIONS: The silence expression of P2X7R by RNA interference effectively decreases the levels of IL-1ß and TNF-α released by microglia and promotes microglia to phagocytose Aß. P2X7R could be used as an effective therapeutic target for RNA interference treatment of Alzheimer's disease.

[Effects of low-dose X-ray on morphology of neuron and expression of microtubule associated protein-2 in hippocampus of young rats].

OBJECTIVE: To explore the effects of a continuous low-dose of X-ray upon neuronal morphology and expression of microtubule associated protein-2 (MAP-2) in hippocampus of young rats. METHODS: A total of 18 Sprague-Dawley rats aged 35 days were randomly divided into two irradiated groups and one control group (n = 6 each). The irradiated groups received different doses of 0.2 mGy/d, 1.0 mGy/d for 7 consecutive days while the control group sham radiation. The hippocampal pyramidal cell was observed by HE staining, the expression of MAP-2 by immunohistochemistry and Western blot, and the morphologies of microtubule and synapse in CA1 by electron microscopy. RESULTS: (1) The phenomenon of neurodegeneration was observed in the 1.0 mGy group while the control and 0.2 mGy groups were normal; (2) the average optical density of positive MAP-2 protein significantly decreased in the 1.0 mGy group (0.242 ± 0.017) in the region of CA1 versus the control group (0.282 ± 0.016) (F = 14.419, P = 0.005). And the average optical density of positive MAP-2 significantly increased in the 0.2 mGy group (0.331 ± 0.017) compared with the control group (F = 21.700, P = 0.002). The expression of total MAP-2 significantly decreased in the 1.0 mGy group (0.332 ± 0.001) versus the control group (0.370 ± 0.012) (F = 28.055, P = 0.000). And the expression of total MAP-2 significantly increased in the 0.2 mGy group (0.455 ± 0.018) versus the control group (F = 61.974, P = 0.002); (3) there were the reduction of microtubule and the damage of postsynaptic density (PSD) in the 1.0 mGy group in hippocampal CA1. Increased microtubule and normal synapses were found in the 0.2 mGy group in hippocampal CA1. CONCLUSION: The expression of MAP-2 is strongly associated with the integrity of hippocampal neurons in young rats. The 0.2 mGy group may promote the proliferation of hippocampal microtubule in hippocampus and further promote the expression of MAP-2. And the damage of microtubule and PSD on neuron could reduce the expression of MAP-2 in the 1.0 mGy group.

[Small-worldness of functional networks in Alzheimer's disease].

OBJECTIVE: To construct the functional networks of human brains by resting-state functional magnetic resonance imaging (fMRI) and examine whether or not the small-world property of functional brain networks changes in patients with Alzheimer disease (AD). METHODS: A total of 33 AD patients and 20 healthy old volunteers were recruited. Their cognitive functions were evaluated by the mini-mental state examination (MMSE) and Mattis dementia rating scale (DRS). The resting-state BOLD-fMRI data were acquired and preprocessed. Then the correlation coefficient of every pair of 90 regions was calculated and correlation matrix Z (N×N, N = 90) generated by Fisher Z transformation. The small-world property of functional brain networks was tested for AD patients and normal elders according to the definition of small-worldness. The changes of relevant parameters in AD patients were examined by two sample t-tests. RESULTS: Behavioral results: the MMSE scores of AD group and normal controls (NOR) were 20.60 ± 2.30 and 28.20 ± 1.80 respectively. The DRS scores of AD and NOR groups were 96.00 ± 10.82 and 123.22 ± 13.74 respectively. The MMSE and DRS scores were statistically different between two groups. Calculation of small-world parameters: Within the range of 0.1 ≤ Sparsity ≤ 0.4, both groups satisfied the small-world property. However, the clustering coefficient Cp and the average shortest path Lp of AD group were significantly higher than those of NOR group at each threshold (P < 0.05). CONCLUSIONS: The functional brain networks in AD patients still have the property of small-world. But the levels of Cp and Lp are higher in AD patients than those in normal controls. It suggests that the capacity of information transmission in functional brain networks and the ability of information integration in different brain regions in AD patients are impaired. This finding is of great importance in elucidating the pathological mechanisms of AD from the viewpoint of networks.

[The comparative study on high field MRI and pathology of Alzheimer's disease transgenic mice].

OBJECTIVE: To observe and investigate the neuroimaging characters in early progression of transgenic Alzheimer's disease (AD) mice model, and make sure the diagnosis value of 7.0 T high field magnetic resonance microimaging (MRMI). METHODS: APP/PS-1 transgenic mice aged 3, 6, 9 months and the same aged wild type mice were each divided into 6 groups (6 mice in every groups) based on age. The mice brains were scaned with 7.0T high magnetic field MR. Then the mice were killed. The Aß immunohistochemistry examination was analyzed in the mice brains specimens, and pathological changes were in comparison with the T(2) weighted imaging in the mice brains. RESULTS: There were a few Aß plaques in the brains of 6 months APP/PS-1 transgenic mice, while Aß plaques were increased both in number and volume in the cerebral cortex and hippocampus of 9 months AD mice. The brains of APP/PS-1 double transgenic mice of 3, 6 months and the control group mice were not showed intensity loss on T(2) weighted MR images, while the signal intensity loss was visualized in the cerebral cortex and hippocampus of 9 months AD mice. CONCLUSION: 7.0T high magnetic field MR could display Aß plaques in the brains of APP/PS-1 double transgenic mice of 9 months and it is helpful to diagnosis early AD.

[Central mechanism of electric-acupuncture at Zusanli (ST36) for gastric mucous membrane protection with FMRI].

OBJECTIVE: To explore the central mechanism of acupuncture in protecting gastric mucous membrane by a composite analysis of gastric mucous membrane related indices in peripheral blood and functional MRI (fMRI) signal changes after electric-acupuncturing Zusanli (ST36) acupoint. METHODS: Sixteen healthy adult volunteers were divided into true acupoint group (A) and sham acupoint group (B). Zusanli acupoint was used for Group A. Peripheral blood was drawn 5 min before and 5, 15, 25, 30 min after needle-removal for the detection of gastric mucous membrane related indices. fMRI was performed during acupuncture and the acquired fMRI data were analyzed by SPM2 (P < 0.001). RESULTS: The levels of calcitonin gene related peptide (CGRP) and prostaglandin E2 (PGE2) increased while those of endothelin (ET) and gastrin (GAS) decreased significantly after acupuncture in Group A (P < 0.01). And there was no significant change in Group B (P > 0.05). Acupuncturing Zusanli activated the bilateral middle frontal gyrus, caudate, left precentral and postcentral gyri, hypothalamus, anterior cingulate cortex, right hippocampus, insula and cerebellar hemisphere. But acupuncturing the sham acupoint only activated the paracentral lobule and cerebellar hemisphere. CONCLUSION: Acupuncturing Zusanli acupoint activates certain cortex areas and multiple systems to stimulate the release of neurotransmitters and regulate the peripheral humoral factors to achieve the protection of gastric mucous membrane.

[Study of bone mesenchymal stem cells tropism for hepatic tumors and effect on the form of tumor stromal].

OBJECTIVE: To investigate the tropism capacity of the rat bone mesenchymal stem cells (BMSC) for hepatic tumors microenvironment and the effect on the form of tumor stromal. METHODS: Rat BMSC were isolated, cultured and expanded, then incubated with superparamagnetic iron oxide (SPIO) nanoparticles. Prussian blue stain was performed for showing intracellular irons. Walker-256 cells were injected into the rat livers directly to establish hepatic tumor models. The experiment was divided into two experimental groups (the group venous injected with BMSC after tumors becoming mass: tail venous injected with BMSC after MR showed the presence of tumors at 6-8 days after operation and the group venous injected with BMSC before tumors becoming mass: tail venous injected with BMSC when MR showed no presence of tumors at 3 days after operation) and one control group. To the experimental groups animals, MRI was made before venous injection of BMSC and at 5, 10, 15 days after BMSC transplantation. The rats were killed at corresponding period. The pathologic examinations were analyzed, including HE, Prussian blue stain. The expression of vascular endothelial growth factor (VEGF), CD31, von Willebrand factor (vWF) in the specimens harvested at 10 days after BMSC transplantation were detected immunohistochemically. RESULTS: Prussian blue staining of SPIO labeled BMSC demonstrated cells could be effectively labeled and the labeling efficiency was almost 90%. After BMSC transplantation, two experimental groups were showed tuberculous signal intensity loss at the margin of tumors on T(2) weighted MR images at 5, 10 days after transplantation and the signal intensity loss was not visualized at 15 days after transplantation. The control group was not observed signal intensity decrease. Prussian blue staining of histological analysis showed blue-stained iron particles distributed at the margin of tumor at 5, 10, 15 days after transplantation. Immunohistochemical examination showed that the expression of VEGF, CD31, vWF in two experimental groups at 10 days after transplantation were higher than that in the control group (F = 34.03, P < 0.01; F = 84.24, P < 0.01; F = 7.08, P < 0.05). CONCLUSION: Rat BMSC have the ability to migrate towards hepatic tumors in vivo and promote to form vascular endothelium.

[The effect of continuous low doses X-ray on the proliferation of pyramidal cell in hippocampus CA1 in prenatal rats].

OBJECTIVE: To explore the effect of low doses X-ray on proliferation of hippocampal pyramidal cell in the area of CA1 in prenatal rat and its relevant mechanism. METHODS: A total of 25 pregnant rats were randomly divided into four experimental groups and one control group. The experimental groups, in a duration of consistent 18 days, respectively received different doses as follows: 0.015 mGy/d, 0.03 mGy/d, 0.06 mGy/d and 0.09 mGy/d. The control group received sham radiation. To observe the density and width of hippocampal pyramidal cell in the area of CA1 by HE stained and observe the expression of the ERK1/2 by IHM. RESULTS: (1) Except C group, all other groups presented increment in width of the level of hippocampal pyramidal cell, compared with C group; H group, M group, L1 group and L2 group were higher than that (F value respectively were 8.475, 33.42, 14.395, 44.955; P value respectively were 0.002, 0.048, 0.030, 0.012). But the phenomenon of inhomogeneity in width in H group was observed, at the same time, the density of cell in H group became looser (F = 4.466, P = 0.017). (2) The expression of ERK1/2 in the hippocampus CA1 was seen in cytoplasm of every group, the average optical density of positive ERK1/2 protein significantly increased in L1 group and L2 group, compared with control group respectively (F value respectively were 4.561, 4.103, P value respectively were 0.044, 0.035). CONCLUSION: Low doses X-ray could promote proliferation of hippocampus CA1 cell in prenatal. The reason could be the increment of the ERK1/2 protein induced by X-ray. When the doses reached 0.09 mGy/d, the excesses proliferation phenomenon was observed.

Brain hemodynamic changes in amnestic mild cognitive impairment measured by pulsed arterial spin labeling.

We used pulsed arterial spin labeling (PASL) to investigate differences in cerebral blood flow (CBF) between 26 patients with amnestic mild cognitive impairment (aMCI) and 27 controls with normal cognition (NC). Hypoperfusion was observed in the right temporal pole of the middle temporal gyrus and the right inferior temporal gyrus in the aMCI compared with NC group. Interestingly, hyperperfusion was observed in the left temporal pole of the middle temporal gyrus, left superior temporal gyrus, bilateral precuneus, postcentral gyrus, right inferior parietal lobule, and right angular gyrus in the aMCI group, which likely resulted from a compensatory mechanism to maintain advanced neural activities. We found that mean CBF in the right inferior temporal gyrus, precuneus, and postcentral gyrus was positively correlated with cognitive ability in the aMCI but not NC group. Collectively, our data indicate that PASL is a useful noninvasive technique for monitoring changes in CBF and predicting cognitive decline in aMCI.

The impact of age on incremental elastic modulus and incremental compliance of pig hepatic portal vein for liver xenotransplantation.

BACKGROUND: Pigs are currently considered the most likely source of organs for human xenotransplantation because of anatomical and physiological similarities to humans, and the relative ease to be bred in large numbers. Along with the fast development of the genetic engineering and organ transplant immunity medical science, the research of liver xenotransplantation suffers the very big valuing in recent years. Whether the livers from different species after transplanting can perform the normal function, depends on the function regeneration and lucid rates of hepatic portal vein. The objective of this study was to investigate the age effect on biomechanical properties of pig hepatic portal vein to pave the way for seeking a reliable biomaterial for future pig-to-human liver xenotransplantation. METHODS: The biomechanical remodelling of the hepatic portal vein of pigs for 1,2,3,4,5 and 6 months (n = 6 per month) were measured in this study. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The incremental modulus (Einc), the longitudinal incremental modulus (Ep), the circumferential incremental modulus (Ev), incremental compliance (C) and wall thickness were calculated based on the recorded pressure-diameter curves from experimental data. RESULTS: The incremental modulus, pressure strain modulus and the volume modulus of the pig hepatic portal vein increases with the age increased (P < 0.01), while the compliance decreased with the increasing of the age (P < 0.01). CONCLUSIONS: Our present study suggests that the biomechanical properties of the pig hepatic portal vein are age dependent, the pig hepatic portal vein with biomechanical properties that match those of human hepatic portal vein should be chosen for liver xenotransplantation.

Role of myo-inositol by magnetic resonance spectroscopy in early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice.

BACKGROUND/AIMS: To explore the potential value of myo-inositol (mIns), which is regarded as a biomarker for early diagnosis of Alzheimer's disease, in APP/PS1 transgenic (tg) mice detected by (1)H-MRS. METHODS: (1)H-MRS was performed in 30 APP/PS1 tg mice and 20 wild-type (wt) littermates at 3, 5 and 8 months of age. Areas under the peak of N-acetylaspartate (NAA), mIns and creatine (Cr) in the frontal cortex and hippocampus were measured, and the NAA/Cr and mIns/Cr ratios were analyzed quantitatively. RESULTS: Compared with the wt mice, the mIns/Cr ratio of the 3-month-old tg mice was significantly higher (p < 0.05), and pathology showed activation and proliferation of astrocytes in the frontal cortex and hippocampus. The concentration of NAA was significantly lower at 8 and 8 months of age (p < 0.05). According to the threshold of mIns/Cr that was adopted to separate the tg from the wt mice, the rate of correct predictions was 82, 94 and 95%, respectively, for 3, 5 and 8 months. CONCLUSION: Of the early AD metabolites as detected by (1)H-MRS, mIns is the most valuable marker for assessment of AD. Quantitative analysis of mIns may provide important clues for early diagnosis of AD.

Telomerase activity (TMA) in tumour and peritumoural tissues in a rat liver cancer model.

PURPOSE: To study the levels of telomerase activity (TMA) in tumour and peritumoural tissues in a liver cancer model in rats, and to study the change in TMA expression over time. METHODS: Using the telomeric repeated amplification protocol (TRAP), TMA was measured in tumour tissue, peritumoural tissue and normal liver tissue of Walker-256 tumour-bearing rats at 4, 6 and 8 days after tumour implantation. RESULTS: TMA at day 4, 6 and 8 was 0.767+/-0.117, 0.768+/-0.118 and 0.774+/-0.111 in tumour tissue, 0.389+/-0.263, 0.492+/-0.253 and 0.584+/-0.239 in peritumoural tissue, and 0.231+/-0.022, 0.229+/-0.022 and 0.233+/-0.021 in normal liver tissue, respectively. TMA in tumour tissue was higher than that in peri-tumour and normal liver tissues at all time points of measurement (P < 0.05). The TMA levels in tumour tissue and normal liver tissue did not show any change over time. TMA level in the peritumoural tissue increased with time; TMA level in animals sacrificed at day 8 was higher than that seen in animals sacrificed at day 4 (P < 0.05). CONCLUSION: TMA in walker-256 tumour-bearing rats was higher than that in normal and peritumoural tissues. TMA level in the peritumoural tissue increased with time suggesting that TMA activation in peritumoural tissue may be an important factor promoting tumour growth.