Study of 320-Slice Dynamic Volume CT Perfusion in Different Pathologic Types of Kidney Tumor: Preliminary Results

Objective

To investigate microcirculatory differences between pathologic types of kidney tumor using 320-slice dynamic volume CT perfusion.

Methods

Perfusion imaging with 320-slice dynamic volume CT was prospectively performed in 85 patients with pathologically proven clear cell renal cell carcinoma (RCC) (n = 66), papillary RCC (n = 7), chromophobe RCC (n = 5), angiomyolipoma (AML) with minimal fat (n = 7), or RCC (n = 78). Equivalent blood volume (Equiv BV), permeability surface-area product (PS; clearance/unit volume = permeability), and blood flow (BF) of tumor and normal renal cortex were measured and analyzed. Effective radiation dose was calculated.

Results

There was a significant difference in all three parameters between tumor and normal renal cortex (P<0.001). Equiv BV was significantly different between RCC and AML with minimal fat (P = 0.038) and between clear cell RCC and AML with minimal fat (P<0.001). Mean Equiv BV and BF were significantly higher in clear cell RCC than in papillary RCC (P<0.001 for both) and mean Equiv BV was higher in clear cell RCC than in chromophobe RCC (P<0.001). The effective radiation dose of the CT perfusion protocol was 18.5 mSv.

Conclusion

Perfusion imaging using 320-slice dynamic volume CT can be used to evaluate hemodynamic features of the whole kidney and kidney tumors, which may be useful in the differential diagnosis of these four pathologic types of kidney tumor.     

Assessment of Renal Function in Patients with Unilateral Ureteral Obstruction Using Whole-Organ Perfusion Imaging with 320-Detector Row Computed Tomography

Background

Obstructed nephropathy is a common complication of several disease processes. Accurate evaluation of the functional status of the obstructed kidney is important to achieve a good outcome. The purpose of this study was to investigate renal cortical and medullary perfusion changes associated with unilateral ureteral obstruction (UUO) using whole-organ perfusion imaging with 320-detector row computed tomography (CT).

Methodology/Principle Findings

Sixty-four patients with UUO underwent whole-organ CT perfusion imaging. Patients were divided into 3 groups, mild, moderate, and severe, based on hydronephrosis severity. Twenty sex- and age-matched patients without renal disease, who referred to abdominal CT, were chosen as control subjects. Mean cortical and medullary perfusion parameters of obstructed and contralateral kidneys were compared, and mean perfusion ratios between obstructed and contralateral kidneys were calculated and compared. Mean cortical or medullary blood flow (BF) and blood volume (BV) of the obstructed kidneys in the moderate UUO and BF, BV, and clearance (CL) in the severe UUO were significantly lower than those of the contralateral kidneys (p < 0.05). The mean cortical or medullary BF of the obstructed kidney in the moderate UUO, and BF, BV, and CL in the severe UUO were significantly lower than those of the kidneys in control subjects (p < 0.05). Mean cortical or medullary BF of the non-obstructed kidneys in the severe UUO were statistically greater than that of normal kidneys in control subjects (p < 0.05). An inverse correlation was observed between cortical and medullary perfusion ratios and grades of hydronephosis (p < 0.01).

Conclusions/Significance

Perfusion measurements of the whole kidney can be obtained with 320-detector row CT, and estimated perfusion ratios have potential for quantitatively evaluating UUO renal injury grades.     

Correlation between CT Perfusion Parameters and Microvessel Density and Vascular Endothelial Growth Factor in Adrenal Tumors

We evaluated the correlation between computed tomography (CT) perfusion parameters and markers of angiogenesis in adrenal adenomas and non-adenomas to determine if perfusion CT can be used to distinguish between them. Thirty-four patients with pathologically-confirmed adrenal tumors (17 adenomas, 17 non-adenomas) received CT perfusion imaging before surgery. CT perfusion parameters (blood flow [BF], blood volume [BV], mean transit time [MTT], and permeability surface area product [PS]) were calculated. Tumor tissue sections were examined with immunohistochemical methods for vascular endothelial growth factor (VEGF) expression and microvessel density (MVD). The mean age of the 34 patients was 43 years. The median BV was significantly higher in adenomas than in non-adenomas [12.3 ml/100 g, inter-quartile range (IQR): 10.4 to 16.5 ml/100 g vs. 8.8 ml/100 g, IQR: 3.3 to 9.4 ml/100 g, p = 0.001]. Differences in BF, MTT, and PS parameter values between adenomas and non-adenomas were not significant (p>0.05). The mean MVD was significantly higher in adenomas compared to non-adenomas (98.5±28.5 vs. 53.5±27.0, p<0.0001). Adenomas also expressed significantly higher median VEGF than non-adenomas (65%, IQR: 50 to 79% vs. 45%, IQR: 35 to 67%, p = 0.02). A moderately strong correlation between BF and VEGF (r = 0.53, p = 0.03) and between BV and MVD among adenomas (r = 0.57, p = 0.02) exist. Morphology, MVD, and VEGF expression in adenomas differ significantly from non-adenomas. Of the CT perfusion parameters examined, both BF and BV correlate with MVD, but only BF correlates with VEGF, and only in adenomas. The significant difference in BV suggests that BV may be used to differentiate adenomas from non-adenomas. However, the small difference in BV shows that it may only be possible to use BV to identify adenomas vs. non-adenomas at extreme BV values.     

CXCR7 Silencing Attenuates Cell Adaptive Response to Stromal Cell Derived Factor 1α after Hypoxia

Previous studies have shown that chemotactic factor stromal-cell derived factor 1α (SDF1α) promotes cell recovery from hypoxic injury via its main receptor C-X-C chemokine receptor type (CXCR) 4. However, the role of its new receptor CXCR7 on cell repair against hypoxia and cell response to SDF1α remains largely unknown. In this study, neurons induced from hippocampal progenitor cells were pre-conditioned in hypoxia for 4h and subsequently monitored to investigate the function of SDF1α on cell repair after hypoxia. Neurons were assessed for their cell morphology, actin filament polymerization and migration capability. SDF1α protein levels increased significantly 1 h after hypoxia compared to control (P<0.01), and it reached a peak at 24 h after hypoxia. Moreover, addition of SDF1α promoted neurite outgrowth and actin filament polymerization both in normoxic and hypoxic cells compared to untreated cells. Cell migration showed a time-dependent increase with SDF1α stimulation in both groups, and hypoxic cells illustrated a significant augment at 0.5 h, 1 h and 12 h after SDF1α application compared to normoxic cells (P<0.01). CXCR7 expression also increased with time dependence after hypoxia and demonstrated a two-fold upregulation compared to control at 24 h after hypoxia. With CXCR7 silencing, axon elongation and actin filament polymerization induced by SDF1α were inhibited sharply both in normoxic and hypoxic cells. CXCR7 silencing also leads to reduced hypoxic cell migration at 0.5 h, 1 h, 12 h, 24 h and 36 h after SDF1α application (P<0.01), but it failed to reduce normoxic cell migration induced by SDF1α at 0.5 h, 1 h and 12 h (P>0.05). 24 h SDF1α stimulation led to higher ERK1/2 phosphorylation compared to control, and ERK1/2 phosphorylation increased more in hypoxic cells than that in normoxic cells. This study suggested that CXCR7 plays an important role on cell repair processing induced by SDF1α, and CXCR7 silencing attenuates cell adaptive response to acute SDF1α stimulation (≤12 h) after hypoxia.     

Hypoxia and vitamin D differently contribute to leptin and dickkopf-related protein 2 production in human osteoarthritic subchondral bone osteoblasts

Introduction

Bone remodelling and increased subchondral densification are important in osteoarthritis (OA). Modifications of bone vascularization parameters, which lead to ischemic episodes associated with hypoxic conditions, have been suspected in OA. Among several factors potentially involved, leptin and dickkopf-related protein 2 (DKK2) are good candidates because they are upregulated in OA osteoblasts (Obs). Therefore, in the present study, we investigated the hypothesis that hypoxia may drive the expression of leptin and DKK2 in OA Obs.

Methods

Obs from the sclerotic portion of OA tibial plateaus were cultured under either 20% or 2% oxygen tension in the presence or not of 50 nM 1,25-dihydroxyvitamin D₃ (VitD₃). The expression of leptin, osteocalcin, DKK2, hypoxia-inducible factor 1α (Hif-1α) and Hif-2α was measured by real-time polymerase chain reaction and leptin production was measured by enzyme-linked immunosorbent assay (ELISA). The expression of Hif-1α, Hif-2α, leptin and DKK2 was reduced using silencing RNAs (siRNAs). The signalling pathway of hypoxia-induced leptin was investigated by Western blot analysis and with mitogen-activated protein kinase (MAPK) inhibitors.

Results

The expression of leptin and DKK2 in Obs was stimulated 7-fold and 1.8-fold, respectively (P <0.05) under hypoxia. Interestingly, whereas VitD₃ stimulated leptin and DKK2 expression 2- and 4.2-fold, respectively, under normoxia, it stimulated their expression by 28- and 6.2-fold, respectively, under hypoxia (P <0.05). The hypoxia-induced leptin production was confirmed by ELISA, particularly in the presence of VitD₃ (P <0.02). Compared to Obs incubated in the presence of scramble siRNAs, siHif-2α inhibited VitD₃-stimulated leptin mRNA and protein levels by 70% (P =0.004) and 60% (P <0.02), respectively, whereas it failed to significantly alter the expression of DKK2. siHif-1α has no effect on these genes. Immunoblot analysis showed that VitD₃ greatly stabilized Hif-2α under hypoxic conditions. The increase in leptin expression under hypoxia was also regulated, by p38 MAPK (P <0.03) and phosphoinositide 3-kinase (P <0.05). We found that the expression of leptin and DKK2 were not related to each other under hypoxia.

Conclusions

Hypoxic conditions via Hif-2 regulation trigger Obs to produce leptin, particularly under VitD₃ stimulation, whereas DKK2 is regulated mainly by VitD₃ rather than hypoxia.     

肾脏肿瘤患者CT灌注参数与肾功能生化检测指标的相关性研究

目的:探讨肾脏肿瘤患者CT灌注参数与肾功能生化检测指标的相关性。方法:选取河北省第六人民医院2013年3月至2018年1月期间收治的35例肾脏肿瘤患者作为观察组,另选取同期来我院体检的35例健康者作为对照组,均对两组受试者实施CT灌注成像,获取等效血容量(Equiv BV)、表面渗透性(Ps)、血流量(BF)等CT灌注参数,并检测两组受试者血尿素氮(BUN)、血肌酐(Scr)、总胆固醇(TC)、甘油三酯(TG)等肾功能生化指标,对比两组受试者上述指标检测结果,采用Pearson相关分析CT灌注参数与肾功能生化指标的相关性。结果:与对照组相比,观察组CT灌注参数Equiv BV、Ps、BF均降低,肾功能生化指标BUN、Scr、TC、TG水平均升高,有统计学差异(P0.05)。Pearson相关分析结果显示,CT灌注参数Equiv BV、Ps、BF与肾功能生化指标TC、BUN均呈负相关(P0.05),与Scr、TG无相关性(P0.05)。结论:肾脏肿瘤患者的CT灌注参数Equiv BV、Ps、BF均较低,BUN、Scr、TC、TG水平均较高,且CT灌注参数与BUN、TC水平呈负相关性,可作为评估肾脏肿瘤患者肾功能的辅助方法。     

Impact of Bacterial Vaginosis,as Assessed by Nugent Criteria and Hormonal Status on Glycosidases and Lectin Binding in Cervicovaginal Lavage Samples

The objective of this study was to evaluate the impact of hormonal status and bacterial vaginosis (BV) on the glycosidases present and glycosylation changes as assessed by lectin binding to cervicovaginal lavage constituents. Frozen cervicovaginal lavage samples from a completed study examining the impact of reproductive hormones on the physicochemical properties of vaginal fluid were utilized for the present study. In the parent study, 165 women were characterized as having BV, intermediate or normal microflora using the Nugent criteria. The presence of glycosidases in the samples was determined using quantitative 4-methyl-umbelliferone based assays, and glycosylation was assessed using enzyme linked lectin assays (ELLA). Women with BV had elevated sialidase, α-galactosidase, β-galactosidase and α-glucosidase activities compared to intermediate or normal women (P<0.001, 0.003, 0.006 and 0.042 respectively). The amount of sialic acid (Sambucus nigra, P = 0.003) and high mannose (griffithsin, P<0.001) were reduced, as evaluated by lectin binding, in women with BV. When the data were stratified according to hormonal status, α-glucosidase and griffithsin binding were decreased among postmenopausal women (P<0.02) when compared to premenopausal groups. These data suggest that both hormonal status and BV impact the glycosidases and lectin binding sites present in vaginal fluid. The sialidases present at increased levels in women with BV likely reduce the number of sialic acid binding sites. Other enzymes likely reduce griffithsin binding. The alterations in the glycosidase content, high mannose and sialic acid binding sites in the cervicovaginal fluid associated with bacterial vaginosis may impact susceptibility to viruses, such as HIV, that utilize glycans as a portal of entry.     

Clinicopathological Characteristics of Gynecological Cancer Associated with Hypoxia-Inducible Factor 1α Expression: A Meta-Analysis Including 6,612 Subjects

BackgroundGynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1α (HIF-1α) in gynecological cancer remains unclear.MethodElectronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched from inception through October 2014 for published, case-control studies assessing the association between HIF-1α and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines.ResultsOur meta-analysis, which included 6,612 women, demonstrated that the expression of HIF-1α was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39, p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001; cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression of HIF-1α in III‒IV stage or lymph node metastasis was significantly higher than that in I‒II stage or that without lymph node metastasis, respectively (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p<0.0001). HIF-1α was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2: OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI): 1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95% (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95% (CI): 2.48,12.31, p<0.0001).ConclusionHIF-1α is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.     

Hypoxia-inducible Factor-1α (HIF-1α) Protein Diminishes Sodium Glucose Transport 1 (SGLT1) and SGLT2 Protein Expression in Renal Epithelial Tubular Cells (LLC-PK1) under Hypoxia

In this work, we demonstrated the regulation of glucose transporters by hypoxia inducible factor-1α (HIF-1α) activation in renal epithelial cells. LLC-PK₁ monolayers were incubated for 1, 3, 6, or 12 h with 0% or 5% O₂ or 300 μm cobalt (CoCl₂). We evaluated the effects of hypoxia on the mRNA and protein expression of HIF-1α and of the glucose transporters SGLT1, SGLT2, and GLUT1. The data showed an increase in HIF-1α mRNA and protein expression under the three evaluated conditions (p < 0.05 versus t = 0). An increase in GLUT1 mRNA (12 h) and protein expression (at 3, 6, and 12 h) was observed (p < 0.05 versus t = 0). SGLT1 and SGLT2 mRNA and protein expression decreased under the three evaluated conditions (p < 0.05 versus t = 0). In conclusion, our results suggest a clear decrease in the expression of the glucose transporters SGLT1 and SGLT2 under hypoxic conditions which implies a possible correlation with increased expression of HIF-1α.     

Intravoxel Incoherent Motion Diffusion Weighted MR Imaging for Monitoring the Instantly Therapeutic Efficacy of Radiofrequency Ablation in Rabbit VX2 Tumors without Evident Links between Conventional Perfusion Weighted Images

ObjectiveTo investigate the intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) as a potential valuable marker to monitor the therapy responses of VX2 to radiofrequency ablation (RF Ablation).MethodsThe institutional animal care and use committee approved this study. In 10 VX2 tumor–bearing rabbits, IVIM-DWI examinations were performed with a 3.0T imaging unit by using 16 b values from 0 to 800 sec/mm². The true diffusion coefficient (D), pseudodiffusion coefficient (D^*) and perfusion fraction (f) of tumors were compared between before and instantly after RF Ablation treatment. The differences of D, D^* and f and conventional perfusion parameters (from perfusion CT and dynamic enhanced magnetic resonance imaging, DCE-MRI) in the coagulation necrosis area, residual unablated area, untreated area, and normal control had been calculated by compared t- test. The correlation between f or D^* with perfusion weighted CT including blood flow, BF (milliliter per 100 mL/min), blood volume, BV (milliliter per 100 mL/min), and capillary permeability–surface area, PMB (as a fraction) or from DCE-MRI: transfer constant (K_trans), extra-vascular extra-cellular volume fraction (V_e) and reflux constant (K_ep) values had been analyzed by region-of-interest (ROI) methods to calculate Pearson’s correlation coefficients.ResultsIn the ablated necrosis areas, f and D^* significantly decreased and D significantly increased, compared with residual unblazed areas or untreated control groups and normal control groups (P < 0.001). The IVIM-DWI derived f parameters showed significant increases in the residual unablated tumor area. There was no significant correlations between f or D^* and conventional perfusion parameters.ConclusionsThe IVIM-DW derived f, D and D^* parameters have the potential to indicate therapy response immediately after RF Ablation treatment, while no significant correlations with classical tumor perfusion metrics were derived from DCE-MRI and perfusion-CT measurements.     

Tumor Secretion of CCL22 Activates Intratumoral Treg Infiltration and Is Independent Prognostic Predictor of Breast Cancer

It has been reported that dense intratumoral infiltration of Foxp3 ⁺Tregs (Tregs) was an independent factor for poor prognosis of breast cancer (BC) patients. However, the cytokines activating the Treg infiltration are not known. This study was undertaken to evaluate the role of CCL22 and TGF-β1 in this cascade and their prognostic significance for BC patients. 417 cases of invasive breast cancer were selected from the prior study cohort and the expressions of CCL22 and TGF-β1 were assessed by immunohistochemistry. It was identified that tumor secretion of CCL22 was positively correlated with the intratumoral Treg infiltration (P<0.0001), but its association with lymphoid aggregates surrounding the tumor was not proven to be significant (P=0.056). Moreover, CCL22 expression was found to be associated with the tumor histological features known to be related with unfavorable prognosis of patients, including high histological grade (P<0.0001), negative ER (P<0.0001), negative PR (P=0.001), and HER2 amplification (P=0.028). Similar to intratumoral Treg infiltrates, CCL22 tumor secretion correlated with the prognosis of the molecular subtypes of breast carcinoma (P<0.0001). Univariate analysis revealed CCL22 to be an independent prognostic factor for overall survival (OS, P<0.0001) and progression-free survival (PFS, P<0.0001) of BC patients that were confirmed by multivariate analysis (P=0.011 and P=0.010 respectively). In contrast, although TGF-β1 expression was positively correlated with both Tregs infiltrates into the tumor bed and lymphoid aggregates surrounding the tumor (P=0.023; P=0.046, respectively), its expression was not significantly associated with the molecular subtypes of breast carcinoma and the prognosis of the patients. Our study indicates that both CCL22 and TGF-β1 are candidate chemoattractants for intratumoral Foxp3 ⁺Tregs infiltration; however, unlike the later, CCL22 is an independent prognostic predictor of BC patients, and it therefore may have the potential to serve as a target for immunotherapeutic strategy of BC.     

Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative

Introduction

Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD.

Methods

Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUV_max), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with β-coefficients (β) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors.

Results

Vascular inflammation (measured as SUV_max) was greater (P < 0.001) in patients with sacroiliitis (mean ± SD = 7.33 ± 2.09) defined by CT compared to those without sacroiliitis (6.39 ± 1.49, P = 0.038). There were associations between PsA and aortic inflammation (β = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (β = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (χ² = 124.6, P < 0.001).

Conclusions

Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings.

Electronic supplementary material

The online version of this article (doi:10.1186/ar4676) contains supplementary material, which is available to authorized users.     

Association between CXCL10 and DPP4 Gene Polymorphisms and a Complementary Role for Unfavorable IL28B Genotype in Prediction of Treatment Response in Thai Patients with Chronic Hepatitis C Virus Infection

Pretreatment serum levels of interferon-γ-inducible protein-10 (IP-10, CXCL10) and dipeptidyl peptidase-4 (DPP IV) predict treatment response in chronic hepatitis C (CHC). The association between functional genetic polymorphisms of CXCL10 and DPP4 and treatment outcome has not previously been studied. This study aimed to determine the association between genetic variations of CXCL10 and DPP4 and the outcome of treatment with pegylated interferon-α (PEG-IFN-α) based therapy in Thai patients with CHC. 602 Thai patients with CHC treated using a PEG-IFN-α based regimen were genotyped for CXCL10 rs56061981 G>A and IL28B rs12979860 C>T. In addition, in patients infected with CHC genotype 1, DPP4 (rs13015258 A>C, rs17848916 T>C, rs41268649 G>A, and rs 17574 T>C) were genotyped. Correlations between single nucleotide polymorphisms, genotype, and treatment response were analyzed. The rate of sustained virologic response (SVR) was higher for the CC genotype of IL28B rs12979860 polymorphisms than for non-CC in both genotype 1 (60.6% vs. 29.4%, P < 0.001) and non-genotype 1 (69.4% vs. 49.1%, P < 0.05) CHC. SVR was not associated with the CXCL10 gene variant in all viral genotypes or DPP4 gene polymorphisms in viral genotype1. Multivariate analysis revealed IL28B rs12979860 CC genotype (OR = 3.12; 95% CI, 1.72–5.67; P < 0.001), hepatitis C virus RNA < 400,000 IU/ml (OR = 2.21; 95% CI, 1.22–3.99, P < 0.05), age < 45 years (OR = 2.03; 95% CI, 1.11–3.68; P < 0.05), and liver fibrosis stage 0–1 (OR = 1.64; 95% CI, 1.01–2.65, P < 0.05) were independent factors for SVR. Unfavorable IL28B rs12979860 CT or TT genotypes with the CXCL10 rs56061981 non-GG genotype were associated with a higher SVR than GG genotype (66.7% vs. 33.0%, P = 0.004) in viral genotype 1. In Thai CHC genotype 1 infected patients with an unfavorable IL28B rs12979860 CT/TT genotype, the complementary CXCL10 polymorphism strongly enhances prediction of treatment response.     

Personality,Perceived Environment,and Behavior Systems Related to Future Smoking Intentions among Youths: An Application of Problem-Behavior Theory in Shanghai,China

Background

Smoking among youths is a worldwide problem, particularly in China. Many endogenous and environmental factors influence smokers’ intentions to smoke; therefore, a comprehensive model is needed to understand the significance and relationship of predictors. This study aimed to develop a prediction model based on problem-behavior theory (PBT) to interpret intentions to smoke among Chinese youths.

Methods

We conducted a cross-sectional study of 26,675 adolescents from junior, senior, and vocational high schools in Shanghai, China. Data on smoking status, smoking knowledge, attitude toward smoking, parents’ and peers’ smoking, and media exposure to smoking were collected from students. A structural equation model was used to assess the developed prediction model.

Results

The experimental smoking rate and current smoking rate among the students were 11.0% and 3%, respectively. Our constructed model showed an acceptable fit to the data (comparative fit index = 0.987, root-mean-square error of approximation = 0.034). Intention to smoke was predicted by perceived environment (β = 0.455, P < 0.001) system consisting of peer smoking (β = 0.599, P < 0.001), parent smoking (β = 0.152, P < 0.001), and media exposure to smoking (β = 0.226, P < 0.001), and behavior system (β = 0.487, P < 0.001) consisting of tobacco experimentation (β = 0.663, P < 0.001) and current smoking (β = 0.755, P < 0.001). Smoking intention was irrelevant for personality system in students (β = -0.113, P>0.05) which consisted of acceptance of tobacco use (β = 0.668, P < 0.001) and academic performance (β = 0.171, P < 0.001).

Conclusion

The PBT-based model we developed provides a good understanding of the predictors of intentions to smoke and it suggests future interventions among youths should focus on components in perceived environment and behavior systems, and take into account the moderating effects of personality system.     

Comparison of SPECT/CT and MRI in Diagnosing Symptomatic Lesions in Ankle and Foot Pain Patients: Diagnostic Performance and Relation to Lesion Type

PurposeThe purpose of this study was to compare the diagnostic performance of SPECT/CT and MRI in patients with ankle and foot pain, with regard to the lesion types.ResultsIn overall lesions, the sensitivity, PPV and NPV of SPECT/CT for symptomatic lesions were 93%, 56%, 91%, and they were 98%, 48%, 95% for MRI. There was no significant difference between SPECT/CT and MRI. However, the specificity of SPECT/CT was significantly higher than that of MRI (48% versus 24%, P = 0.016). Uptake grade on SPECT/CT was significantly higher in symptomatic lesions (P < 0.001), and its area under curve on ROC analysis was 0.787. In the analysis of each lesion type, the specificity of SPECT/CT was poor in joint lesions compared with other lesion types and MRI (P < 0.001, respectively). MRI exhibited lower specificity than SPECT/CT in bone lesions (P = 0.004) and ligament/tendon lesions (P < 0.001).ConclusionsSPECT/CT has MRI-comparable diagnostic performance for symptomatic lesions in ankle and foot pain patients. SPECT/CT and MRI exhibit different diagnostic specificity in different lesion types. SPECT/CT may be used as a complementary imaging method to MRI for enhancing diagnostic specificity.     

Regulation of α-Transducin and α-Gustducin Expression by a High Protein Diet in the Pig Gastrointestinal Tract

BackgroundThe expression of taste receptors (TASRs) and their signalling molecules in the gastrointestinal (GI) epithelial cells, including enteroendocrine cells (EECs), suggests they participate in chemosensing mechanisms influencing GI physiology via the release of endocrine messengers. TASRs mediate gustatory signalling by interacting with different transducers, including α-gustducin (G_αgust) and α-transducin (G_αtran) G protein subunits. This study tested whether G_αtran and G_αgust immunoreactive (-IR) cells are affected by a short-term (3 days) and long-term (30 days) high protein (Hp) diet in the pig GI tract.ResultIn the stomach, G_αgust and G_αtran-IR cells contained serotonin (5-HT) and ghrelin (GHR), while in the small and large intestine, G_αgust and G_αtran-IR colocalized with 5-HT-, cholecystokinin (CCK)- and peptide YY (PYY)-IR. There was a significant increase in the density of G_αtran-IR cells in the pyloric mucosa in both short- and long-term Hp diet groups (Hp3 and Hp30) vs. the control group (Ctr) (P<0.05), while the increase of G_αgust-IR cells in the pyloric mucosa was significant in Hp30 group vs. Ctr and vs. Hp3 (P<0.05); these cells included G_αtran / 5HT-IR and G_αtran / GHR-IR cells (P<0.05 and P<0.001 vs. Ctr, respectively) as well as G_αgust /5-HT-IR or G_αgust / GHR-IR cells (P<0.05 and P<0.01 vs. Ctr, respectively). In the small intestine, we recorded a significant increase in G_αtran-IR cells in the duodenal crypts and a significant increase of G_αgust-IR cells in the jejunal crypts in Hp3 group compared to HP30 (P<0.05). With regard to the number of G_αtran-G_αgust IR cells colocalized with CCK or 5-HT, there was only a significant increase of G_αtran / CCK-IR cells in Hp3 group compared to Ctr (P = 0.01).ConclusionThis study showed an upregulation of selected subpopulations of G_αgust / G_αtran-IR cells in distinct regions of the pig GI tract by short- and long-term Hp diet lending support to TASR-mediated effects in metabolic homeostasis and satiety mechanisms.     

New Insights in Abdominal Pain in Paroxysmal Nocturnal Hemoglobinuria (PNH): A MRI Study

Introduction

Abdominal pain in PNH has never been investigated by in-vivo imaging studies. With MRI, we aimed to assess mesenteric vessels flow and small bowel wall perfusion to investigate the ischemic origin of abdominal pain.

Materials and Methods

Six PNH patients with (AP) and six without (NOP) abdominal pain underwent MRI. In a blinded fashion, mean flow (MF, quantity of blood moving through a vessel within a second, in mL·s^-1) and stroke volume (SV, volume of blood pumped out at each heart contraction, in mL) of Superior Mesenteric Vein (SMV) and Artery (SMA), areas under the curve at 60 (AUC₆₀) and 90 seconds (AUC₉₀) and K^trans were assessed by two operators.

Results

Mean total perfusion and flow parameters were lower in AP than in NOP group. AUC₆₀: 84.81 ± 11.75 vs. 131.73 ± 18.89 (P < 0.001); AUC₉₀: 102.33 ± 14.16 vs. 152.58 ± 22.70 (P < 0.001); K^trans: 0.0346 min^-1 ± 0.0019 vs. 0.0521 ± 0.0015 (P = 0.093 duodenum, 0.009 jejunum/ileum). SMV: MF 4.67 ml/s ± 0.85 vs. 8.32 ± 2.14 (P = 0.002); SV 3.85 ml ± 0.76 vs. 6.55 ± 1.57 (P = 0.02). SMA: MF 6.95 ± 2.61 vs. 11.2 ± 2.32 (P = 0.07); SV 6.52 ± 2.19 vs. 8.78 ± 1.63 (P = 0.07). We found a significant correlation between MF and SV of SMV and AUC₆₀ (MF:ρ = 0.88, P < 0.001; SV: ρ = 0.644, P = 0.024), AUC₉₀ (MF: ρ = 0.874, P < 0.001; SV:ρ = 0.774, P = 0.003) and K^trans (MF:ρ = 0.734, P = 0.007; SV:ρ = 0.581, P = 0.047).

Conclusions

Perfusion and flow MRI findings suggest that the impairment of small bowel blood supply is significantly associated with abdominal pain in PNH.     

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.     

The Association of Platelet Count with Clinicopathological Significance and Prognosis in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

ObjectiveElevated platelet count (PC), a measure of systemic inflammatory response, is inconsistently reported to be associated with poor prognosis in patients with renal cell carcinoma (RCC). We conducted a systematic review and meta-analysis to clarify the significance of PC in RCC prognosis.MethodsPubMed, Embase, and Web of Science databases were searched to identify eligible studies to evaluate the associations of PC with patient survival and clinicopathological features of RCC.ResultsWe analyzed 25 studies including 11,458 patients in the meta-analysis and categorized the included articles into three groups based on RCC stage. An elevated PC level was associated with poor overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87-2.67, P<0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48, P<0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI 2.41-10.73, P<0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34, P<0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, P<0.001) for metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, P = 0.038), CSS (HR 3.38, 95% CI 1.86-6.15, P<0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, P = 0.002) for clear cell RCC. Furthermore, an elevated PC level was significantly associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, P = 0.001), pathological T stage (OR 3.13, 95% CI 2.60-3.77, P<0.001), lymph node metastasis (OR 4.01, 95% CI 2.99-5.37, P<0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, P<0.001), Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, P<0.001), tumor size (OR 4.69, 95% CI 2.78-7.91, P<0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI 3.26-9.28, P<0.001).ConclusionAn elevated PC level implied poor prognosis in patients with RCC and could serve as a readily available biomarker for managing this disease.