Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.     

盐酸山莨菪碱对噪声暴露后耳蜗琥珀酸脱氢酶活性的影响

目的：观测豚鼠在噪声暴露后不同时间内盐酸山莨菪碱（６５４－２０防治组和损伤组的耳蜗琥珀酸脱氢酶（ＳＤＨ）活性变化,探讨噪声暴露后ＳＤＨ活性的变化趋势以及６５４－２在噪声暴露中对ＳＤＨ活性的影响。方法：把豚鼠分成对照组、损伤组与６５４－２防治组,在噪声暴露后不同时期,用Ｎａｃｈｌａｓ四唑氮盐法及图象分析仪显示并测算ＳＤＨ活性。结果：在噪声暴露后第３天,各组酶活性损伤最重。各组耳蜗ＳＤＨ活性第１、２回     

复方益心汤对大鼠心血管的保护作用

用小牛血清及高脂饮食制成大鼠实验性动脉粥样硬化模型，观察中药益心汤对动脉内膜，心肌形态及酶组化的影响。结果显示益心汤可使冠状动脉内膜损伤得以修复，心肌变性改善，心肌细胞内SDH和ATPase数量增加。     

Anti-glycative and anti-inflammatory effects of protocatechuic acid in brain of mice treated by d-galactose

Protocatechuic acid (PCA) at 0.5%, 1% or 2% was supplied to d-galactose (DG) treated mice for 8 week. PCA intake at 2% increased its deposit in brain. DG treatment increased brain level of reactive oxygen species, protein carbonyl, carboxymethyllysine, pentosidine, sorbitol, fructose and methylglyoxal (P < 0.05). PCA intake, at 1% and 2%, lowered brain level of these parameters (P < 0.05). DG treatments enhanced activity and protein expression of aldose reductase (AR) and sorbitol dehydrogenase, as well as declined glyoxalase I (GLI) activity and protein expression (P < 0.05). PCA intake at 1% and 2% reduced activity and protein expression of AR (P < 0.05), and at 2% restored GLI activity and expression (P < 0.05). DG injection also elevated cyclooxygenase (COX)-2 activity and expression, and increased the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E₂ in brain (P < 0.05). PCA intake decreased these cytokines (P < 0.05), and at 1% and 2% suppressed COX-2 activity and expression (P < 0.05). PCA intake at 1% and 2% also lowered DG-induced elevation in activity, mRNA expression and protein production of nuclear factor kappa B p65 (P < 0.05). These findings suggest that the supplement of protocatechuic acid might be helpful for the prevention or alleviation of aging.     

糖尿病人群不同类型高血压发病率及影响因素的研究

目的 探讨糖尿病人群不同类型高血压的发病率及影响因素。方法 选择基线血压正常的糖尿病患者2367例,观察平均25.6月后进展为不同类型高血压的发病率及影响因素。 结果 进展为单纯收缩期高血压（ISH）、单纯舒张期高血压（IDH）及收缩期-舒张期双期高血压（SDH）的标化发病率（/1000人年）分别为80.2、89.2、130.8,男性为81.7、97.9、145.6,女性为66.8、55.6、80.3。影响糖尿病人群进展为ISH的危险因素是年龄、SBP及BMI （RR分别为2.409、2.757、1.807,P〈0.05）;进展为IDH的危险因素是男性、DBP、BMI、SUA（RR分别为2.064、1.771、1.569、1.463,P〈0.05）;进展为IDH的保护因素是年龄、糖尿病病程5年以上（RR分别为0.809、0.552,P〈0.05）;进展为SDH的危险因素是男性、SBP、BMI、TG、LDL-C（RR分别为1.882、2.720、1.549、1.284、1.410,P〈0.05）。 结论 糖尿病人群SDH的标化发病率最高,高血压各亚型发病影响因素不同,且有性别差异。     

Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys

We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27-33 yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16-22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at ~27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was ~1.6 fold greater in VL from CR animals compared to Control animals at ~27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETS(ab)), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETS(ab) fiber CSA and determined that CR fibers respond differently to the challenge of mitochondrial deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals.     

Placement of a subdural evacuating port system for management of iatrogenic hyperacute subdural hemorrhage following intracranial monitor placement

A 22-year-old man was admitted with a severe traumatic brain injury developed a hyperacute subdural hematoma (SDH) following attempted brain tissue oxygen monitor placement. This patient was successfully treated by placement of a subdural evacuation portal system (SEPS). The patient presented to a Level I trauma center after a severe bike versus auto accident. On admission, he was found to have a Glasgow Coma Scale (GCS) score of 3. The patient had small areas of intraparechymal hemorrhage as well as suspicion for diffuse axonal injury in the midbrain. Based on the patient’s GCS score, neurological monitoring was indicated as a part of his intensive care unit treatment, however a SDH occurred during an attempted placement of a brain tissue oxygen monitor. This iatrogenic hyperacute SDH after burr hole monitoring device placement was treated with a SEPS drain. The SEPS drain has been shown to provide complete and/or temporary decompression of liquefied SDH. To our knowledge, this is the first report of using the SEPS to treat iatrogenic SDH associated with an intracranial monitoring device. This technique should be added to the armament of treatment options for a neurosurgeon to treat or temporize a hyperacute SDH with increased intracranial pressure in specific patients.     

Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABA_A receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog > human > rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.