Zhongqiu Wang

Contrast-enhanced dynamic and diffusion-weighted MR imaging at 3.0 T to assess aggressiveness of bladder cancer

BACKGROUND Diffusion weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have been considered useful for pathological staging and histological grading in bladder cancer. To our knowledge, no study has combined the two imaging modalities together to assess aggressiveness of bladder cancer. OBJECTIVE To assess the clinical aggressiveness of bladder cancer with DCE MRI and DWI at 3.0T. MATERIALS AND METHODS A total of 59 patients with 69 pathologically confirmed tumor lesions were included in this study. All patients underwent MR examination at 3.0T basing on DWI and DCE imaging. Tumor staging and histological grade were evaluated. The aggressiveness of bladder cancer was classified as low-, intermediate-, or high-aggressiveness according to its pathological phenotype. Apparent diffusion coefficient (ADC) value and semi-quantitative parameters (wash-in rate and wash-out rate) were determined. The correlation between clinical aggressiveness and ADC value, wash-in rate and wash-out rate were analyzed. In addition, the diagnostic accuracy of the diffusion and semi-quantitative parameters were estimated using receiver operating characteristic curve (ROC). RESULTS Aggressiveness of bladder cancer is negatively correlated with ADC value (r=-0.705, p<0.0001) and wash-out rate (r=-0.719, p<0.0001). The tumor ADC value is positively correlated with wash-out rate (r=0.555, p<0.0001). The diagnostic specificity and accuracy using tumor ADC value and wash-out for the tumor with size <24mm were better than that tumors with size ≥24mm. The sensitivity, specificity and accuracy of ADC and wash-out rate in combination in diagnosis of bladder cancer aggressiveness were 96.7%, 94.9% and 95.7%, respectively. ROC curve revealed the diagnostic performance of aggressiveness of bladder cancer using ADC value and wash-out rate were 0.928 (cut-off value: 0.905×10(-3)mm(2)/s) and 0.891 (cut-off value: 0.685min(-1)), respectively. CONCLUSION ADC and wash-out rate derived from DWI and DCE-MRI at 3.0T have good potential to assess the aggressiveness of bladder cancer and the accuracy was greater for ADC than for semi-quantitative parameters.

Osteoblast–osteoclast interactions

ABSTRACT Bone homeostasis depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts. Imbalance of this tightly coupled process can cause diseases such as osteoporosis. Thus, the mechanisms that regulate communication between osteoclasts and osteoblasts are critical to bone cell biology. It has been shown that osteoblasts and osteoclasts can communicate with each other through direct cell–cell contact, cytokines, and extracellular matrix interaction. Osteoblasts can affect osteoclast formation, differentiation, or apoptosis through several pathways, such as OPG/RANKL/RANK, RANKL/LGR4/RANK, Ephrin2/ephB4, and Fas/FasL pathways. Conversely, osteoclasts also influence formation of bones by osteoblasts via the d2 isoform of the vacuolar (H+) ATPase (v-ATPase) V0 domain (Atp6v0d2), complement component 3a, semaphorin 4D or microRNAs. In addition, cytokines released from the resorbed bone matrix, such as TGF-β and IGF-1, also affect the activity of osteoblasts. Drugs could be developed by enhancing or restricting some of these interactions. Several reviews have been performed on the osteoblast–osteoclast communication. However, few reviews have shown the research advances in the recent years. In this review, we summarized the current knowledge on osteoblast–osteoclast communication.

Daily variation in global and local DNA methylation in mouse livers.

DNA methylation is one of the best-characterized epigenetic modifications and has an important biological relevance. Here we showed that global DNA methylation level in mouse livers displayed a daily variation where the peak phases occurred during the end of the day and the lowest level at the beginning of the day in the light-dark or dark-dark cycles. Typical repeat sequence long interspersed nucleotide element-1 (LINE-1) had a similar methylation rhythm to global DNA. DNA methyltransferase 3A (DNMT3A) and ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) brought a relative forward daily variation to global DNA methylation, and the temporary change in ratio of SAM to SAH had no influence on the DNA methylation level. The rhythm of global DNA methylation was lost and DNA methylation level was increased in Per1-/-Per2-/- double knockout mice, which were in accordance with changes of Dnmt3a mRNA levels and its rhythm. Our results suggest that the daily variation in global DNA methylation was associated with the change of Dnmt3a expression rather than ratio of SAM to SAH.

Benchmark dose estimation of cadmium reference level for hypertension in a Chinese population

Cadmium exposure can cause high blood pressure or hypertension. Benchmark dose has been used to estimate the reference point of cadmium for kidney and bone damage. In this study, we observed the association of blood pressure and cadmium in blood (BCd) and evaluated the reference level of cadmium for hypertension using benchmark dose (BMD) approach. A total of 441 subjects were included in this study. Blood samples were collected from each individual for BCd determination. Blood pressure was measured by electronic sphygmomanometer. BMD and BMDL were calculated using BMD software corresponding to additional risk of 10%. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and prevalence of hypertension increased with the increasing of BCd, especially for SBP (χ(2)=3.9, p=0.047 in men; χ(2)=4.3, p=0.037 in women). With a benchmark response of 10%, the BMDL10 for hypertension (high SBP) was 0.95μg/L and 1.02μg/L for women and men, respectively; the BMDL10 for hypertension (high DBP) was 1.8μg/L and 1.66μg/L for women and men, respectively. Our data evidenced that BCd was associated with elevation in blood pressure and hypertension, especially for women. The reference level of cadmium for hypertension with high SBP was lower than that of high DBP.

Effects of lead and cadmium co-exposure on hemoglobin in a Chinese population

Cadmium (Cd) and lead (Pb) show adverse effects on hemoglobin. But most studies are focussed on one single agent. In this study, we observed the main and interactive effects of Cd and Pb on the hemoglobin level in a Chinese population. A total of 308 persons (202 women and 106 men), living in controlled and polluted areas, were included in this study. Blood and urine were collected to determine the levels of hemoglobin (Hb), Cd, Pb, and urinary N-acetyl-β-D-glucosaminidase (UNAG). The Cd and Pb level of subjects living in the polluted area were significantly higher compared to those living in the control area (p<0.05). The level of hemoglobin was declined with the increasing BPb (p<0.05) and BCd in women. The Hb of women and men with the highest level of BCd and BPb were decreased by 8.3g/L and 10.7 g/L compared to those with the lowest level of BCd and BPb, respectively. The Hb level of those women and men with the highest level of UNAG decreased by 4.2g/L and 17.2g/L compared with those with low level of UNAG, respectively. Hb was negatively associated with BPb, BCd, and UNAG. This study evidenced that Cd and Pb can influence Hb level. In addition, our study shows that Cd and Pb may have interactive effects on Hb and Hb level was correlated with tubular dysfunction caused by Cd and Pb exposure.

Emodin suppresses cadmium-induced osteoporosis by inhibiting osteoclast formation

Environmental level of cadmium (Cd) exposure can induce bone loss. Emodin, a naturally compound found in Asian herbal medicines, could influence osteoblast/osteoclast differentiation. However, the effects of emodin on Cd-induced bone damage are not clarified. The aim of this study was to investigate the role of emodin on Cd-induced osteoporosis. Sprague-Dawley male rats were divided into three groups which were given 0mg/L, 50mg Cd/L and 50mg Cd/L plus emodin (50mg/kg body weight). Bone histological investigation, microCT analysis, metabolic biomarker determination and immunohistochemical staining were performed at the 12th week. The bone mass and bone microstructure index of rats treated with Cd were obviously lower than in control. Cd markedly enhanced the osteoclast formation compared with control. Emodin significantly abolished the Cd-induced bone microstructure damage (p<0.05), osteoclast formation and increase of tartrate-resistant acid phosphatase 5b level (p<0.05). Our data further showed that emodin attenuated the Cd-induced inhibition of osteoprotegerin expression and stimulation of receptor activator for nuclear factor-κ B ligand expression. Our data show that emodin suppresses the Cd-induced osteoporosis by inhibiting osteoclast formation.

Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage.

Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing.

Pancreatic neuroendocrine neoplasms at magnetic resonance imaging: comparison between grade 3 and grade 1/2 tumors

Background The grading of pancreatic neuroendocrine neoplasms (PanNENs) is associated with the choice of treatment strategy. The aim of this study is to identify the magnetic resonance imaging (MRI) features in differentiating pancreatic neuroendocrine tumors (PanNETs) grade 1/2 (G1/G2) and pancreatic neuroendocrine carcinoma grade 3 (PanNEC G3). Patients and methods A total of 59 patients with histologically proven PanNENs and who underwent pretreatment MRI were retrospectively analyzed. Tumor location, size, boundary, cystic or solid appearance, enhancement degree, pancreatic duct dilatation, metastases and MRI signal were evaluated. Apparent diffusion coefficients (ADCs) were measured on ADC maps. Receiver operating characteristic curve was used to determine the cut off values and the sensitivity and specificity of prediction. Spearman correlation and logistic regression analysis were adopted to identify the association between MRI features and pathological parameters. Results A total of 47 lesions were PanNETs G1/G2 and 12 lesions were PanNEC G3. G1/G2 tumors were more common with well-circumscribed border compared with PanNEC G3. Ill- defined boundary, big size, necrosis, low-moderate enhancement, pancreatic duct dilatation, metastases and high diffusion-weighted imaging (DWI) intensity were more common in PanNEC G3 than in PanNETs G1/G2. The ADC values of PanNEC G3 were also significantly lower compared with the PanNETs G1/G2 and normal pancreatic parenchyma. The cut off value of ADC was 0.95×10−3 mm2/s for differentiating PanNEC G3 from PanNETs G1/G2 with 72.3% sensitivity and 91.6% specificity, respectively. Ki-67 index and mitosis count positively correlated with tumor size, pancreatic duct dilatation and metastases (P<0.05) and negatively correlated with ADC values (P<0.01), respectively. Regression analysis further showed that metastases and ADC value were associated with PanNENs grade. Conclusion Metastases and ADC value may have potential for differentiating PanNEC G3 from PanNETs G1/G2.

Differentiation of pancreatic neuroendocrine carcinoma from pancreatic ductal adenocarcinoma using magnetic resonance imaging: The value of contrast-enhanced and diffusion weighted imaging

Pancreatic neuroendocrine carcinoma (PNEC) is often misdiagnosed as pancreatic ductal adenocarcinoma (PDAC). This retrospective study differentiated PNEC from PDAC using magnetic resonance imaging (MRI), including contrast-enhanced (CE) and diffusion-weighted imaging (DWI). Clinical data and MRI findings, including the T1/T2 signal, tumor boundary, size, enhancement degree, and apparent diffusion coefficient (ADC), were compared between 37 PDACs and 13 PNECs. Boundaries were more poorly defined in PDAC than PNEC (97.3% vs. 61.5%, p<0.01). Hyper-/isointensity was more common in PNEC than PDAC at the arterial (38.5% vs. 0.0), portal (46.2% vs. 2.7%) and delayed phases (46.2% vs. 5.4%) (all p<0.01). Lymph node metastasis (97.3% vs. 61.5%, p<0.01) and local invasion/distant metastasis (86.5% vs. 46.2%, p<0.01) were more common in PDAC than PNEC. Enhancement degree via CE-MRI was higher in PNEC than PDAC at the arterial and portal phases (p<0.01). PNEC ADC values were lower than those of normal pancreatic parenchyma (p<0.01) and PDAC (p<0.01). Arterial and portal phase signal intensity ratios and ADC values showed the largest areas under the receiver operating characteristic curve and good sensitivities (92.1%–97.2%) and specificities (76.9%–92.3%) for differentiating PNEC from PDAC. Thus the enhancement degree at the arterial and portal phases and the ADC values may be useful for differentiating PNEC from PDAC using MRI.

Value of diffusion‑weighted magnetic resonance imaging in predicting World Health Organization grade in G1/G2 pancreatic neuroendocrine tumors

The present study aimed to investigate the value of diffusion-weighted magnetic resonance imaging (DWI) in the grading of well-differentiated pancreatic neuroendocrine tumors (PanNETs). A total of 44 patients with histologically proven well-differentiated PanNET [grade 1 (G1) and grade 2 (G2) according to the World Health Organization (WHO) criteria] underwent pretreatment magnetic resonance imaging (MRI), which was retrospectively analyzed. The location, size, cystic or solid appearance, boundary, presence or absence of tumor contrast enhancement, and MRI signal of the tumor were assessed. Apparent diffusion coefficients (ADCs) within the primary tumor were measured on ADC maps. Receiver operating characteristic curves were used to determine ADC cut-off values and the sensitivity and specificity of the grade prediction. Spearmans rank correlation was utilized to probe the association between ADC value and PanNET grade or pathological parameters. G1 tumors exhibited a well-circumscribed border more often than G2 tumors. No marked differences were observed between PanNET G1 and PanNET G2 for cystic or solid appearance, enhancement, and T1- and T2-weighted imaging signals. Marked hyperintensities were more common in PanNET G2 tumors than in PanNET G1 tumors (P<0.01). The mean ADC values were statistically different between the normal pancreas and G1 and G2 tumors (P<0.01), and between PanNET G1 and PanNET G2 (P<0.05). Correlation analysis showed that ADC value was negatively correlated with PanNET grade, mitotic count and Ki-67 proliferation index (P<0.05). The cut-off ADC value was 0.930×10−3 mm2/sec, which identified G2 tumors with 82.4% sensitivity and 79.5% selectivity. ADC value therefore represents a non-invasive and valuable imaging parameter in predicting the WHO grade of tumors in well-differentiated PanNET.