Multimodal data integration using machine learning to predict the risk of clear cell renal cancer metastasis: a retrospective multicentre study.

PURPOSE: To develop and validate a predictive combined model for metastasis in patients with clear cell renal cell carcinoma (ccRCC) by integrating multimodal data. MATERIALS AND METHODS: In this retrospective study, the clinical and imaging data (CT and ultrasound) of patients with ccRCC confirmed by pathology from three tertiary hospitals in different regions were collected from January 2013 to January 2023. We developed three models, including a clinical model, a radiomics model, and a combined model. The performance of the model was determined based on its discriminative power and clinical utility. The evaluation indicators included area under the receiver operating characteristic curve (AUC) value, accuracy, sensitivity, specificity, negative predictive value, positive predictive value and decision curve analysis (DCA) curve. RESULTS: A total of 251 patients were evaluated. Patients (n = 166) from Shandong University Qilu Hospital (Jinan) were divided into the training cohort, of which 50 patients developed metastases; patients (n = 37) from Shandong University Qilu Hospital (Qingdao) were used as internal testing, of which 15 patients developed metastases; patients (n = 48) from Changzhou Second People's Hospital were used as external testing, of which 13 patients developed metastases. In the training set, the combined model showed the highest performance (AUC, 0.924) in predicting lymph node metastasis (LNM), while the clinical and radiomics models both had AUCs of 0.845 and 0.870, respectively. In the internal testing, the combined model had the highest performance (AUC, 0.877) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.726 and 0.836, respectively. In the external testing, the combined model had the highest performance (AUC, 0.849) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.708 and 0.804, respectively. The DCA curve showed that the combined model had a significant prediction probability in predicting the risk of LNM in ccRCC patients compared with the clinical model or the radiomics model. CONCLUSION: The combined model was superior to the clinical and radiomics models in predicting LNM in ccRCC patients.

A therapy that modulates T lymphocyte subsets in patients infected with Epstein-Barr virus: Ganciclovir combined with interferon atomization inhalation.

To investigate the effect of ganciclovir combined with interferon atomization inhalation on T lymphocyte subsets in patients with Epstein-Barr virus (EBV) infection and its efficacy. Fifty patients with EBV infection who received ganciclovir combined with interferon atomization inhalation were selected as the observation group, and 50 healthy people were selected as the control group. The changes of T lymphocyte subsets in peripheral blood were detected by flow cytometry before treatment and at the 1st, 2nd, 3rd and 4th cycle after treatment. Before treatment, the CD3+, CD4+, CD4+/CD8+ indexes of the patients were significantly lower than those of the control group (P < .05), and the CD8+ level was significantly increased (P < .05). After one cycle of treatment, there was no significant difference in the changes of T lymphocyte subsets compared with those before treatment. After 2 and 3 cycles of treatment, CD3+, CD4+, CD4+/CD8+ values were higher than those before treatment (P > .05), and CD8+ index was lower than that before treatment (P < .05). After the 4th cycle of treatment, CD3+, CD4+, CD4+/CD8+ values were significantly improved (P < .05), and CD8+ index was significantly decreased (P < .05). Ganciclovir combined with interferon atomization inhalation can regulate the changes of T lymphocyte subsets in patients with EBV infection, improve the patient's condition, and has no obvious adverse reactions. Monitoring the changes of T lymphocyte subsets during treatment is more meaningful to predict the therapeutic effect of patients with EB virus infection.

Disconnection of Network Hubs Underlying the Executive Function Deficit in Patients with Ischemic Leukoaraiosis.

BACKGROUND: Cognitive impairment is the most common clinical manifestation of ischemic leukoaraiosis (ILA), but the underlying neurobiological pathways have not been well elucidated. Recently, it was thought that ILA is a "disconnection syndrome". Disorganized brain connectome were considered the key neuropathology underlying cognitive deficits in ILA patients. OBJECTIVE: We aimed to detect the disruption of network hubs in ILA patients using a new analytical method called voxel-based eigenvector centrality (EC) mapping. METHODS: Subjects with moderate to severe white matters hyperintensities (Fazekas score ≥3) and healthy controls (HCs) (Fazekas score = 0) were included in the study. The resting-state functional magnetic resonance imaging and the EC mapping approach were performed to explore the alteration of whole-brain network connectivity in ILA patients. RESULTS: Relative to the HCs, the ILA patients exhibited poorer cognitive performance in episodic memory, information processing speed, and executive function (all ps < 0.0125). Additionally, compared with HCs, the ILA patients had lower functional connectivity (i.e., EC values) in the medial parts of default-mode network (i.e., bilateral posterior cingulate gyrus and ventral medial prefrontal cortex [vMPFC]). Intriguingly, the functional connectivity strength at the right vMPFC was positively correlated with executive function deficit in the ILA patients. CONCLUSION: The findings suggested disorganization of the hierarchy of the default-mode regions within the whole-brain network in patients with ILA and advanced our understanding of the neurobiological mechanism underlying executive function deficit in ILA.

Imaging features of dermatofibrosarcoma protuberans.

Aims: The study highlights diffusion-weighted imaging (DWI) and dynamic enhancement features of DFSP and characterizes unenhanced and enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scans. Settings and Design: Image findings and clinical histories of 23 patients with DFSP were reviewed. Nine patients underwent CT before and after intravenous administration of contrast material. MRI was performed for 17 patients. CT and MRI findings were analyzed using location, size, edge, shape, infiltration sign, density and signal enhancement mode, and degree. Results: Patients showed 26 superficial and one deep lesion. Ten superficial lesions bulged onto the skin surface. Fourteen lesions were well-defined and 13 ill-defined. All lesions were nodular, with nine being multilobular. Thirteen showed infiltration to adjacent skin, fat, and fascia. Seven lesions on CT were iso- or hypo-dense to muscle without calcification. Contrast-enhanced CT showed inhomogeneous moderate and progressive enhancement in the arterial phase. Small tortuous vessels were seen in the arterial phase in one case. Sixteen tumors displayed signals that were similar to muscle by T1WI. Ten lesions were either hyper-intense to muscle or iso-intense to fat; the deep DFSP was hypo-intense by T2WI. All lesions were hyper-intense homogeneously or heterogeneously under fat-suppressed T2WI. Twelve superficial lesions showed high-intermediate signal, and one deep lesion showed low-intermediate signal with DWI. Seven cases showed low signal diffusion coefficient (ADC) images. Dynamic enhancement and signal intensity-time (SI-T) curves of four tumors showed rapid SI increases followed by steady or slightly rising SI. All lesions showed inhomogeneous, progressive enhancement in the arterial phase. Conclusions: This report is the first on dynamic curves and highlights DWI and T2WI features of DFSP. DFSP can be correctly diagnosed by combining a patient's clinical manifestations with imaging characteristics.

Long non-coding RNA ANRIL serves as a potential marker of disease risk, inflammation, and disease activity of pediatric inflammatory bowel disease.

BACKGROUND: Long non-coding antisense RNAs in the INK4 locus (lnc-ANRIL) have been reported to be involved in inflammation and immunity. However, few studies have reported its clinical application in pediatric inflammatory bowel disease (IBD). Therefore, we conducted this study to investigate the correlation between lnc-ANRIL expression and disease risk, inflammation, and activity in pediatric IBD patients. METHODS: Pediatric patients with Crohn's disease (CD; n = 40), ulcerative colitis (UC; n = 40), and controls (n = 20) were recruited. For all pediatric IBD patients, lnc-ANRIL expression in peripheral blood mononuclear cells and serum inflammatory cytokine levels were measured by RT-qPCR and ELISA, respectively. For the controls, lnc-ANRIL expression was also measured. RESULTS: Lnc-ANRIL levels were lower in CD (P = 0.002) and UC (P = 0.001) patients compared with the controls; negatively correlated with C-reactive protein levels (P<0.01), erythrocyte sedimentation rate (P<0.01), disease activity (P<0.05), and severity (P<0.05) in CD and UC patients; and inversely associated with tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17, and IL-23 levels in both CD and UC patients (all P<0.01). Further subgroup analyses revealed that the association between lnc-ANRIL and inflammatory cytokines and disease activity was more remarkable in pediatric patients with moderate or severe IBD. CONCLUSION: Lnc-ANRIL may serve as a potential marker for evaluating disease risk and monitoring disease activity in pediatric IBD patients.

Escitalopram attenuates ß-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3ß pathway.

Tau hyperphosphorylation is an important pathological feature of Alzheimer's disease (AD). To investigate whether escitalopram could inhibit amyloid-ß (Aß)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aß1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aß1-42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3ß pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3ß pathway and decreased Aß1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3ß pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aß1-42 induced impairment of neurite outgrowth and spine density, and reversed Aß1-42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aß1-42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3ß pathway.

LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice.

More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients.

Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.

Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3ß in hippocampal extracts. No significant change in the total level of GSK-3ß was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3ß. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3ß signaling pathway.

Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells.

To investigate the effect of escitalopram (a widely used and highly efficacious antidepressant from the SSRI class) on tau hyperphosphorylation, HEK293/tau441 cells were pretreated with 4 µM of forskolin for 2 h. Then we treated the cells with different doses of escitalopram (0, 5, 10, 20, 40, 80 µM) for 22 h. We measured the phosphorylation level of tau by Western blotting. It was shown that escitalopram could protect tau from hyperphosphorylation induced by pharmacological activation of protein kinase A (PKA) at a dose of 20, 40, and 80 µM in vitro. Interestingly, the same dose of escitalopram could also increase the level of serine-9-phosphorylated GSK-3ß (inactive form) and the phosphorylation level of Akt at Ser473 (active form) with no significant change in the level of total GSK-3ß and Akt. Unexpectedly, 5-hydroxytryptamine 1A receptor (5-HT1A) agonist 8-OH-DPAT did not decrease forskolin-induced tau hyperphosphorylation. Our results suggest that escitalopram can ameliorate forskolin-induced tau hyperphosphorylation, which is not through the typical 5-HT1A pathway, and Akt/GSK-3ß signaling pathway is involved. These findings may support an effective role of antidepressants in the prevention of dementia associated with depression in patients.

Glycogen synthase kinase-3 regulates production of amyloid-ß peptides and tau phosphorylation in diabetic rat brain.

The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer's disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-ß peptides (A ß) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And A ß 40 and A ß 42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of A ß overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of A ß and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.

[CT diagnosis of different pathological types of ground-glass nodules].

OBJECTIVE: To explore the CT features of ground-glass nodules (GGN) including preinvasive lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). METHODS: Ninety-seven GGN lesions confirmed by operation pathology were included in this study. The lesions were divided into three groups: preinvasive lesion group (24 cases), MIA group (39 cases), IAC group (34 cases). The lesion size, 3-dimensional ratio, 2-dimensional ratio in axial images, lesion density, shape, speculation, lobulation, air-containing space and pleural indentation on the preoperative CT images in the three groups were analyzed and compared with pathological results. The data were statistically analyzed using SPSS 17.0. RESULTS: All preinvasive lesions presented as pure GGN on CT image, most showed round-like shape, clear and smooth border. MIA presented as pure GGN or mixed GGN on CT image, most showed round-like shape, with a clear and smooth border. IAC most presented as mixed GGN on CT image, often showed irregular shape. Speculation, lobulation, air-containing space and pleural indentation displayed gradually increasing from preinvasive lesions to MIA and IAC. There were statistically significant differences in lesion size, CT density, shape, air-containing space, speculation, pleural indentation and long diameter of solid component between the MIA and IAC groups (P < 0.05 for all). There were statistically significant differences in CT density values and long diameters of solid component of the lesions between the preinvasive lesion group and MIA group (P < 0.05). The AUC of solid component of the preinvasive lesion group and MIA group was 0.705, and that of the MIA and IAC groups was 0.814. CONCLUSION: Comprehensive analysis of the CT image features of GGNs, especially the solid component in the lesions, may help to the preoperative and differential diagnosis of preinvasive lesions, MIA and IAC.

[Diagnostic value of solid component for lung adenocarcinoma shown as ground-glass nodule on computed tomography].

OBJECTIVE: To explore the feasibility of making a preoperative diagnosis of lung adenocarcinoma shown as ground-glass nodule (GGN) on computed tomography (CT). METHODS: A total of 143 GGN lesions proved pathologically were divided randomly into A and B groups. Then each group was further divided pathologically into preinvasive lesion, minimal invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) subgroups. Group A (n = 101), size of lesion, proportion of ground glass opacity (GGO) composition of lesion, long diameter, longest diameter and size of solid component in lesion were measured on CT so as to establish the CT diagnostic standard of lung adenocarcinoma shown as GGN on CT. Group B (n = 42) was employed to evaluate the accuracy of the above CT diagnostic standard. SPSS 17.0 software was used for statistical analysis. RESULTS: Significant statistic significance existed in all parameters among all groups (P < 0.05). All parameters were correlated the pathologic type of lesion. The differences were statistically significant (P = 0.000). Through the receiver operating characteristic (ROC) curve, between groups of preinvasive lesion and MIA, each parameter had a medium diagnostic value of 0.70-0.90; between groups of MIA and IAC, size of lesion and long diameter of solid component in lesion had a medium diagnostic value of 0.70-0.90, longest diameter of solid component, size of solid component in lesion and proportion of GGO composition of lesion had a high diagnostic value with an AUC of >0.90. The CT diagnostic standard, derived from group A, was used to analyze the pathologic type of group B. And t no significant statistic significance existed between CT preoperative diagnosis and operative pathologic diagnosis (P > 0.05) . The correct diagnosis rates of size of lesion, proportion of GGO composition of lesion, long diameter, longest diameter and size of solid component in lesion were 71.43%, 76.19%, 90.05%, 90.05% and 88.10% respectively. CONCLUSION: Based upon size of lesion, proportion of GGO composition of lesion, long diameter, longest diameter and size of solid component in lesion, preoperative CT examination may be used to determine the pathological types of lung adenocarcinoma shown as GGN.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels.

OBJECTIVE: To investigate the relationships between pulmonary ground-glass nodules (GGN) and blood vessels and their diagnostic values in differentiating GGNs. METHODS: Multi-detector spiral CT imaging of 108 GGNs was retrospectively reviewed. The spatial relationships between GGNs and supplying blood vessels were categorized into four types: I, vessels passing by GGNs; II, intact vessels passing through GGNs; III, distorted, dilated or tortuous vessels seen within GGNs; IV, more complicated vasculature other than described above. Relationship types were correlated to pathologic and/or clinical findings of GGNs. RESULTS: Of 108 GGNs, 10 were benign, 24 preinvasive nodules and 74 adenocarcinomas that were pathologically proven. Types I, II, III and IV vascular relationships were observed in 9, 58, 21 and 20 GGNs, respectively. Type II relationship was the dominating relationship for each GGN group, but significant differences were shown among them. Correlation analysis showed strong correlation between invasive adenocarcinoma and type III and IV relationships. Subgroup analysis indicated that type III was more commonly seen in IAC with comparison to type IV more likely seen in MIA. CONCLUSION: Different GGNs have different relationships with vessels. Understanding and recognising characteristic GGN-vessel relationships may help identify which GGNs are more likely to be malignant.

Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.

The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er(3+) nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues.

A Gd-doped Mg-Al-LDH/Au nanocomposite for CT/MR bimodal imagings and simultaneous drug delivery.

The early diagnosis and simultaneous drug delivery monitored by non-invasive visualization are highly challenging but clinical-relevant for the diagnostics and therapy monitoring of serious diseases such as cancers. Herein, a Gd-doped layered double hydroxide (LDH)/Au nanocomposite has been developed as both a drug carrier and a diagnostic agent. The obtained nanocomposite shows high non-anionic anti-cancer drug DOX loading capacity and an interesting pH-responsive release profile of loaded DOX. The nanocomposite was found to be able to efficiently transport DOX into the cancer cell, release the DOX in the acidic cytoplasm and then cause death of cancer cells. Meanwhile, the nanocomposite demonstrates better in vitro CT and T(1)-weighted MR imaging capabilities than the commercial MRI and CT contrast agents and favorable in vivo CT and T(1)-weighted MR imaging performance. After being modified with heparin, the nanocomposite also demonstrates effective CT and MR imagings of tumors by intravenous administration in tumor-bearing mice. Furthermore, the nanocomposite shows negligible cytotoxicity and no detectable tissue damage on mice after injection of high dosage of nanocomposite. In conclusion, the synthetic nanocomposite is expected to be a potential theranostic agent for bimodal imagings of cancers and anti-cancer drug delivery as well.

A NaYbF4: Tm3+ nanoprobe for CT and NIR-to-NIR fluorescent bimodal imaging.

Early diagnosis that combines the high-resolutional CT and sensitive NIR-fluorescence bioimaging could provide more accurate information for cancerous tissues, which, however, remain a big challenge. Here we report a simple bimodal imaging platform based on PEGylated NaYbF(4): Tm(3+) nanoparticles (NPs) of less than 20 nm in diameter for both CT and NIR-fluorescence bioimaging. The as-designed nanoprobes showed excellent in vitro and in vivo performances in the dual-bioimaging, very low cytotoxicity and no detectable tissue damage in one month. Remarkably, the Yb(3+) in the lattice of NaYbF(4): Tm(3+) NPs functions not only as a promising CT contrast medium due to its high X-ray absorption coefficiency, but also an excellent sensitizer contributing to the strong NIR-fluorescent emissions for its large NIR absorption cross-section. In addition, these NPs could be easily excreted mainly via feces without detectable remnant in the animal bodies.

Comparison of adaptive statistical iterative and filtered back projection reconstruction techniques in brain CT.

PURPOSE: To compare image quality and visualization of normal structures and lesions in brain computed tomography (CT) with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP) reconstruction techniques in different X-ray tube current-time products. MATERIALS AND METHODS: In this IRB-approved prospective study, forty patients (nineteen men, twenty-one women; mean age 69.5 ± 11.2 years) received brain scan at different tube current-time products (300 and 200 mAs) in 64-section multi-detector CT (GE, Discovery CT750 HD). Images were reconstructed with FBP and four levels of ASIR-FBP blending. Two radiologists (please note that our hospital is renowned for its geriatric medicine department, and these two radiologists are more experienced in chronic cerebral vascular disease than in neoplastic disease, so this research did not contain cerebral tumors but as a discussion) assessed all the reconstructed images for visibility of normal structures, lesion conspicuity, image contrast and diagnostic confidence in a blinded and randomized manner. Volume CT dose index (CTDI(vol)) and dose-length product (DLP) were recorded. All the data were analyzed by using SPSS 13.0 statistical analysis software. RESULTS: There was no statistically significant difference between the image qualities at 200 mAs with 50% ASIR blending technique and 300 mAs with FBP technique (p>.05). While between the image qualities at 200 mAs with FBP and 300 mAs with FBP technique a statistically significant difference (p<.05) was found. CONCLUSION: ASIR provided same image quality and diagnostic ability in brain imaging with greater than 30% dose reduction compared with FBP reconstruction technique.

Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 µM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

The involvement of upregulation and translocation of phospho-Rb in early neuronal apoptosis following focal cerebral ischemia in rats.

The aim of this study was to investigate the temporal and spatial relationship between phospho-Rb (ser 795) and neuronal apoptotic death in rats subjected to transient focal cerebral ischemia. We found increased phosphorylation of Rb and translocation from neuronal nucleus to cytoplasm in the penumbra zone at 12 h, 1 day, 3 days and 7 days after middle cerebral artery occlusion (MCAO)/reperfusion, compared with sham-operated controls. At 12 h and 1 day, phospho-Rb appeared to be colocalizated with TUNEL staining in neurons, but staining was not colocalizated at 3 days and 7 days. These results demonstrated that cytoplasmic translocation of phospho-Rb from nucleus of neurons occurs in potential apoptotic neurons in the early stages of ischemia/reperfusion, suggesting that the Rb pathway may only be involved in early neuronal apoptosis and may be not an apoptotic signal in the late stages of transient cerebral ischemia.