Differentiating mixed epithelial and stromal tumor family from predominantly cystic renal cell carcinoma using magnetic resonance imaging-based Bosniak classification system version 2019.

PURPOSE: To differentiate mixed epithelial and stromal tumor family (MESTF) of the kidney from predominantly cystic renal cell carcinoma (RCC) using the magnetic resonance imaging (MRI)-based Bosniak classification system version 2019 (v2019). MATERIALS AND METHODS: The study included 36 consecutive patients with MESTF and 77 with predominantly cystic RCC who underwent preoperative renal MRI. One radiologist evaluated and documented the clinical and MRI characteristics (age, sex, laterality, R.E.N.A.L. Nephrometry Score [RNS], surgical approach, the signal intensity on T2-weighted imaging, restricted diffusion and enhancement features in corticomedullary phase). Blinded to clinical and pathological information, another two radiologists independently evaluated Bosniak category of all masses. Interobserver agreement based on Bosniak classification system v2019 was measured by the weighted Cohen/Conger's Kappa coefficient. Furthermore, predominantly cystic RCCs and MESTFs were divided into low (categories I, II, and IIF) and high-class (categories III, and IV) tumors. The independent sample t test (Mann-Whitney U test) or Pearson Chi-square test (Fisher's exact probability test) was utilized to compare clinical and imaging characteristics between MESTFs and predominantly cystic RCCs. The performance of the Bosniak classification system v2019 in distinguishing MESTF from predominantly cystic RCC was investigated via receiver operating characteristic curve analysis. RESULTS: MESTF and predominantly cystic RCC groups significantly differed in terms of age, lesion size, RNS, restricted diffusion, and obvious enhancement in corticomedullary phase, but not sex, laterality, surgical approach, and the signal intensity on T2WI. Interobserver agreement was substantially based on the Bosniak classification system v2019. There were 24 low-class tumors and 12 high-class tumors in the MESTF group. Meanwhile, 13 low-class tumors and 64 high-class tumors were observed in the predominantly cystic RCC group. The distribution of low- or high-class tumors significantly differed between the MESTF and predominantly cystic RCC groups. Bosniak classification system v2019 had excellent discrimination (cutoff value = category III), and an area under curve value was 0.81; accuracy, 80.5%; sensitivity, 87.0%; and specificity, 66.7%. CONCLUSION: The MRI-based Bosniak classification system v2019 can effectively distinguish MESTF from predominantly cystic RCC if category III was used as a cutoff reference.

Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Sevoflurane anesthesia reduces the expression of inflammatory response genes and ß-site amyloid precursor protein-cleaving enzyme in hippocampi of diabetic mice.

Diabetes and inhaled anesthesia are associated with an increased likelihood of developing postoperative cognitive dysfunction in humans and animal models, but the mechanisms are unclear. This study aimed to investigate the effect and mechanism of sevoflurane anesthesia on cognitive function in diabetic (DM) mice. Spontaneously diabetic db/db and control db/m mice were subject to sevoflurane anesthesia or allowed to breathe air, respectively. The Morris water maze test as spatial learning and novel object recognition test as recognition memory were performed. The expression of inflammatory cytokines and neurotoxicity-related genes in the hippocampus of four groups was measured using real-time PCR. The expression level of neurotoxicity and neuroprotection-related proteins in DM mice hippocampus were estimated using Western blot assay. It is found that DM mice developed cognitive impairment; however, the cognitive impairment was not exacerbated in sevoflurane-exposed mice. Sevoflurane anesthesia led to a decrease in mRNA levels of inflammatory cytokines in DM mice hippocampi, including interleukin 17 (IL-17), C-C motif chemokine (CCL20), CCL7 as well as high mobility group box 1 and beta-site amyloid-ß cleaving enzyme 1; and no effect was observed on the expression of neurotoxicity genes, including amyloid precursor protein, choline O-acetyltransferase, tumor necrosis factor, alpha-induced protein 1, B-cell lymphoma 2 and estrogen receptor 2. In addition, we observed elevated phosphorylation of cAMP response element-binding protein in DM mice exposed to sevoflurane anesthesia. In conclusion, sevoflurane did not exacerbate DM-associated cognitive impairment.

The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation.

INTRODUCTION: The aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model. MATERIAL AND METHODS: Forty male Sprague Dawley rats weighing 300-350 g were randomly divided into 5 groups (n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group rats inhaled 3% sevoflurane for 2 h, while the control and DM groups inhaled air. Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg) daily for 4 days, while the control group received intraperitoneal injections of an equal volume of dimethylsulfoxide. The Morris water maze test was performed to test cognition. Animals were killed after the last water maze test and Congo red staining was used to observe deposition of amyloid substance in the hippocampus. The expression of GFAP and IGF-1 in the hippocampus was observed by immunohistochemistry. RESULTS: Diabetes decreased cognition, increased amyloid substance and GFAP expression, and decreased IGF-1 expression in the hippocampus (all p-values < 0.05). Sevoflurane administration intensified and celastrol decreased these changes (all p-values < 0.05). CONCLUSIONS: Sev/DM rats showed cognitive and neurochemical changes similar to those seen in senile dementia. Celastrol decreased these changes and should be evaluated further as a possible clinical agent in dementia.

Evaluation of Neuroprotective Effect of Thymoquinone Nanoformulation in the Rodent Cerebral Ischemia-Reperfusion Model.

The purpose of the present study was to evaluate the neuroprotective efficacy of optimized thymoquinone loaded PLGA-chitosan nanoparticles delivered via nose to brain route in the rodent cerebral ischemia-reperfusion model. The neuroprotective efficacy of the optimized thymoquinone loaded PLGA-chitosan nanoparticles was evaluated in middle cerebral artery occluded rats by various pharmacodynamic and biochemical studies. The pharmacokinetics of thymoquinone loaded PLGA-chitosan nanoparticles in the brain and blood plasma together with qualitative localization of florescent labelled PLGA-chitosan nanoparticles in brain tissues were also determined. Intranasal delivery of optimized thymoquinone loaded PLGA-chitosan nanoparticles (183.5 ± 8.2 nm, 33.63 ± 2.25 mV) to brain significantly reduced the ischemia infarct volume and enhanced the locomotor activity and grip strength in the middle cerebral artery occluded rats. Biochemical studies showed that intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles significantly reduced the lipid peroxidation but elevated the glutathione, catalase, and superoxide dismutase in the brain of middle cerebral artery occluded rats. The pharmacokinetic and localization studies showed that thymoquinone loaded PLGA-chitosan nanoparticles facilitated the delivery of thymoquinone to brain by intranasal nose to brain transport pathways and enhanced their pharmacokinetic profile in brain tissues. Thus, intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles to brain could be potentially used for the neuroprotection and treatment of cerebral ischemia.

Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury.

The diabetic kidney is sensitive to ischemia-reperfusion (I/R) injury due to microvascular complications, such as cellular apoptosis and necrosis. The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). Male rats (N = 40) were randomly assigned to one of five groups: Group A, sham operation; Group B, renal I/R injury; Group C, DM + sham operation; Group D, DM + renal I/R injury; and Group E, DM + sevoflurane pretreatment + renal I/R injury. Sevoflurane pretreatment comprised exposure to 2.5 % sevoflurane for 30 min, followed by exposure to air for 10 min. After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression.

[Relationship between dynamic contrast-enhanced and perfusion magnetic resonance imaging and T-staging of nasopharyngeal carcinoma].

OBJECTIVE: To perform the dynamic contrast-enhanced and perfusion magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) and analyze the correlation with T-staging. METHODS: A total of 46 naïve NPC patients underwent MRI. The parameters of dynamic contrast-enhanced and perfusion MRI included time to peak (TTP), Slopemax and area under the curve (AUC). RESULTS: The increasing period of signal intensity-time curve of all cases was steep. And the perfusion image of AUC could reflect the blood perfusion of tumor tissue. Parameters (TTP/Slopemax/AUC) in different T-staging were T1-staging (60.45/10.59/20 619.56), T2-staging (58.12/12.47/23 037.23), T3-staging (70.61/15.06/26 507.23) and T4-staging (41.72/19.87/30 092.27). Their statistical results were r = -0.247, P > 0.05 and r = 0.859, P < 0.050 and r = 0.963, P < 0.05 respectively. And statistical significance existed in Slopemax, AUC with T-staging. CONCLUSION: Dynamic contrast-enhanced and perfusion MRI can reflect angiogenesis of NPC. And there is a positive correlation between the parameters of dynamic contrast-enhanced and perfusion MRI (Slopemax, AUC) and T-staging.

Protective effect of sevoflurane on hepatic ischaemia/reperfusion injury in the rat: A dose-response study.

BACKGROUND: Ischaemia/reperfusion injury is a common problem in hepatic surgery. An appreciation of the role of sevoflurane dose in preconditioning and subsequent hepatoprotection against ischaemia/reperfusion injury would be useful. OBJECTIVE: The aim of current study was to investigate the protective effect of sevoflurane preconditioning at different doses on hepatic ischaemia/reperfusion injury in rats. DESIGN: Randomised, controlled, laboratory study. SETTING: The Department of Anaesthesiology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China. PARTICIPANTS: Fifty male Sprague-Dawley rats weighing 200 to 250 g, randomly assigned to five groups. INTERVENTIONS: Control group (sham surgery, no ischaemia/reperfusion), I/R group (ischaemia/reperfusion but no sevoflurane pretreatment), S1 [1 minimum alveolar concentration (MAC) = 2.4%], S2 (1.5 MAC = 3.6%) and S3 (2 MAC = 4.8%) groups with sevoflurane pretreatment, respectively, followed by 60 min ischaemia and 120 min reperfusion. MAIN OUTCOME MEASURES: At the end of reperfusion, serum levels of alanine aminotransferase and aspartate aminotransferase as well as superoxide dismutase activity, myeloperoxidase and malondialdehyde content in the liver were determined. Histological examination of the liver was also performed. RESULTS: Serum levels of aspartate aminotransferase and alanine aminotransferase in the sevoflurane groups were significantly reduced compared to the elevated levels seen in the I/R group (P < 0.05). In the liver, the I/R-induced increase in myeloperoxidase activity and malondialdehyde level were significantly reduced by all sevoflurane concentrations (P < 0.05). The decrease in superoxide dismutase activity induced by I/R was prevented by all sevoflurane pretreatments (P < 0.05). No significant differences between the S1, S2 and S3 groups were seen in any of the above variables. CONCLUSION: Sevoflurane pretreatment exerts a protective effect on hepatic ischaemia/reperfusion injury but there is no significant dose-response relationship in the concentration range used. It is possible that a dose-response relationship might exist at lower concentrations.