Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.     

High-Performance Liquid Chromatographic (HPLC) Assay Using Fluorescence Detection for the Simultaneous Determination of Gallopamil and Norgallopamil in Human Plasma

Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.     

C-TIRADS及BRAFV600E基因检测对细针穿刺细胞学难以定性的甲状腺结节的诊断价值

目的 探讨中国版甲状腺影像数据与报告系统（C-TIRADS）、BRAFV600E 基因检测及二者联合对细针穿刺细胞学难以定性的甲状腺结节的诊断价值。方法 纳入我院2020年1月—2021年4月的甲状腺手术患者53例行回顾性分析,术前完成超声、细针穿刺抽吸及BRAFV600E基因检测,选取细针穿刺细胞学难以定性的患者作为研究对象,53例患者共62个结节。以手术病理结果作为金标准,比较C-TIRADS、BRAFV600E基因检测及二者联合诊断对甲状腺结节的诊断效能。结果 C-TIRADS诊断甲状腺癌的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为92.50%、50.00%、77.08%、78.57%、77.42%。BRAFV600E基因诊断甲状腺癌的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为55.00%、100.00%、100.00%、55.00%、70.97%。C-TIRADS联合BRAFV600E基因诊断甲状腺癌的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为95.00%、50.00%、77.55%、84.62%、79.03%。C-TIRADS及联合诊断对甲状腺癌诊断的敏感性高于BRAFV600E基因检测（P<0.001）,BRAFV600E基因检测特异性及阳性预测值高于C-TIRADS及联合诊断（P<0.05）。C-TIRADS、BRAFV600E基因检测及联合诊断对甲状腺癌诊断的阴性预测值和准确性差异无统计学意义（P>0.05）。结论 C-TIRADS及BRAFV600E基因检测对于细胞学难以定性的甲状腺结节均有良好的诊断效能,术前联合应用可以更好地评估甲状腺结节     

Electrical behaviour in a line of anterior pituitary cells (GH cells) and the influence of the hypothalamic peptide, thyrotrophin releasing factor

Anterior pituitary cells of the GH line, which secrete prolactin spontaneously, showed spontaneous action potential activity. Thyrotrophin releasing factor, which increases secretion in these cells, caused a prompt increase of action potential frequency. Potassium, another secretagogue, depolarized the cells and sometimes initiated a burst of action potentials at the onset of this effect. The action potentials persisted in tetrodotoxin-containing and Na-free media, but were suppressed by the Ca-channel blocker, methoxyverapamil. Moreover, elevating the extracellular Ca²⁺ concentration increased the amplitude of the action potentials. These action potentials therefore have a prominent Ca component. This endows them with a particular interest since secretory activity of these cells is known to be dependent on extracellular Ca²⁺. Ba²⁺, which can substitute for Ca²⁺ in maintaining secretion, also substituted for Ca²⁺ in the maintenance of the action potentials. In addition, Ba²⁺ prolonged action potentials remarkably: tetraethylammonium was less effective in this regard.The several parallels between known secretory behaviour and electrical phenomena encourage the view that analysis of electrical activity in anterior pituitary cells may provide useful clues to events involved in stimulus-secretion coupling and in the secretory control exerted by the brain.     

细针穿刺检测BRAFV600E突变丰度与甲状腺乳头状癌临床病理特征的相关性

目的：探讨术前细针穿刺基因检测BRAF^V600E突变丰度与甲状腺乳头状癌(papillary thyroid cancer,PTC)临床病理特征的关系。方法：回顾性统计2021年1月30日至2022年2月28日就诊于南京中医药大学附属中西医结合医院的301例患者临床资料,术前细针穿刺基因检测示BRAF^V600E突变(含突变丰度检测),所有患者完成甲状腺癌根治术,术后病理证实为甲状腺乳头状癌,分析BRAF^V600E基因突变丰度与临床病理特征的关系。结果：纳入301例患者,男91例,女210例,年龄42(33～51)岁,范围18～69岁。肿瘤直径>1 cm的患者BRAF^V600E基因突变丰度高于肿瘤直径≤1 cm者[29.05(18.03～37.56) vs.18.35(6.74～29.61),P<0.001],颈部淋巴结转移患者BRAF^V600E基因突变丰度高于无颈部淋巴结转移者[24.72(8.08～34.32) vs.18(8.68～28.54),P=0.040]...     

Conversion factor for comparison of data from Humphrey and Medmont automated perimeters

Background : Clinical experience has shown that the sensitivity indices reported by the Humphrey Field Analyser (HFA) are generally higher than those given by the Medmont Automated Perimeter (M600). It is the purpose of this paper to determine a conversion factor for the two perimeters and to confirm this prediction using clinical data. Theory predicted that HFA_sensitivity ? 5 dB = M600_sensitivity. Methods : Sensitivity versus eccentricity profiles were measured over the central visual field on 10 young subjects using both perimeters. Results : Both the HFA and the M600 operate within the realms of the Weber law and measure similar Weber fractions. The sensitivity profiles had similar slopes (about ?0.2 dB/degree) and were separated by about six decibels with the HFA reporting higher sensitivity values. This result confirmed the theoretical prediction. Conclusion : The difference in threshold sensitivities between the two perimeters is a result of differences in scaling factors and instrument luminances. A suggested clinical conversion factor is to subtract 5 dB from the HFA data to approximate those of the M600.     

Immunohistochemical and molecular genetic study on epithelioid glioblastoma: Series of seven cases with review of literature

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.