P^53,Bcl—2在皮肤鳞状细胞癌、基底细胞癌脂溢性角化病中联合表达的意义

目的：探讨P^53蛋白,Bcl-2蛋白在皮肤鳞状细胞癌（SCC）,基底细胞癌（BCC）及脂溢性角化病（SK）中的表达及意义。方法：采用S－P法分别对12例SCC,BCC,SK进行免疫组化P^53蛋白,Bcl－2蛋白检测。结果：12例SCC,BCC中分别有9例,11例P^53蛋白表达阳性有10例,11例Bcl-2蛋白表达阳性,12例SK中有1例P^53表达阳性,11例Bcl-2表达阳性,P^53蛋白在SCC,BCC中表达显著高于SK（P＜0．01）。结论：P53蛋白基因突变和Bcl-2蛋白的过度表达（即细胞凋亡机制）在皮肤恶性肿瘤的发生,发展中起重要促进作用。     

Minimal and maximal incidence rates of skin cancer in Caucasians estimated by use of sigmoidal UV dose–incidence curves

BackgroundSigmoidal (S-shaped) dose–cancer incidence relationships are often observed in animal bioassays for carcinogenicity. Ultraviolet (UV) radiation is an established skin carcinogen. The aim of this study is to examine if S-shaped curves describe the relationship between solar UV doses and skin cancer incidences, and if such relationships can be used to estimate threshold levels of non-carcinogenic UV exposure, as well as maximal incidence rates.MethodsWe studied the incidence rate–annual erythema-effective UV dose relationship for squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and cutaneous melanoma (CM) among different Caucasian populations in Europe, Australia and New Zealand.ResultsOur analysis indicates that S-shaped associations describe the data well (P < 0.0001). The age-adjusted incidence rates for cases expected to be due to other causes than solar UV exposure (at zero UV dose) were found to be around 0.6, 9.7 and 4.0 per 100,000 for women in 1997–2007 for SCC, BCC and CM, respectively, and around 1.2, 14.3 and 2.6 per 100,000 for men. The analysis indicates that SCC, BCC and CM have maximal incidence of 361 ± 24, 1544 ± 49 and 36 ± 4 per 100,000 for women, and 592 ± 35, 2204 ± 109 and 50 ± 4 per 100,000 for men.ConclusionsBetween 89 and 95% of the annual CM cases, around 99.8% SCC and 99.4% BCC cases are caused by solar UV exposure. The analysis did not identify any “safe” UV dose below which the risk for skin cancer was absent. Avoidance of UV radiation has a potential to reduce the incidence of skin cancer in fair-skinned population.     

Abnormal motor surround inhibition associated with cortical and deep grey matter involvement in multiple sclerosis

ObjectiveMotor surround inhibition (mSI) is a physiological mechanism that contributes to hand movement control by focusing voluntary movement. Growing evidence suggests that hand movement control is impaired in multiple sclerosis. The aim of the study was to evaluate mSI in MS and to investigate the brain structures involved in mSI in multiple sclerosis.MethodsWe recruited 33 patients and 23 controls. To investigate mSI, we delivered transcranial magnetic single pulses during index finger flexion. Motor evoked potentials were recorded and first dorsal interosseous (“active muscle”) and from the abductor digiti minimi (“surround muscle”). mSI was expressed as the ratio between Motor evoked potentials recorded from the surround muscle during movement and at rest. Participants underwent a magnetic resonance study.ResultsPatients had impaired mSI as compared with controls. Magnetic resonance showed that basal ganglia had smaller volumes and higher mean diffusivity than controls. Impaired mSI correlated with primary motor cortex and basal ganglia involvement in multiple sclerosis.ConclusionAltered mSI in multiple sclerosis is related to cortical and subcortical grey matter involvement.SignificanceOur study provides the first demonstration of a pathophysiological mechanism underlying hand movement control dysfunction in multiple sclerosis. mSI represents a new therapeutic target of multiple sclerosis rehabilitative approaches.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.     

Musical Alexia for Rhythm Notation: A Discrepancy Between Pitch and Rhythm

In the process of reading music, the reading of rhythm and pitch might be differentiated, although there is no evidence of this to date. There have been cases of disorders restricted to the reading of pitch, but none in which the disorder has been restricted to the reading of rhythm. We present a case of musical alexia and agraphia with Wernicke’s aphasia. An in-depth assessment of the subject’s musical reading ability showed that her musical alexia was restricted to unfamiliar melodies. When a melody was divided into rhythm elements and pitch elements, pitch reading was preserved, but rhythm reading was severely disturbed. This is the first case reported of a disorder restricted to rhythm reading, and suggests the independence of rhythm reading and pitch reading.     

Longitudinal study of diffusion tensor imaging properties of affected cortical spinal tracts in acute and chronic hemorrhagic stroke

This study investigated the clinical value of diffusion tensor imaging (DTI) in predicting the motor outcome in patients with basal ganglia hemorrhage. This prospective study included 23 patients assessed with DTI to measure the fractional anisotropy (FA) value in affected cortical spinal tract (CST) at three time points: day 0, day 30 and day 90 after onset. The motor function score (MFS) was applied to evaluate motor function and patients were divided into good and poor outcome groups according to the MFS on day 90. The mean FA value on day 0 was significantly lower in the poor outcome group than in the good outcome group (p < 0.01). FA value gradually decreased in the poor outcome group until day 90 after onset, while it continuously increased in the good outcome group. The MFS obtained at day 90 after onset was significantly correlated with the initial FA value in the affected cerebral peduncle (r = −0.926, p < 0.01). Receiver operating characteristic curve analysis showed that the FA value on day 0 could predict motor function outcome with a sensitivity of 88.89% and specificity of 92.86% at the initial FA value of 0.45. The FA value of affected CST in acute cerebral hemorrhage may valuably predict the motor function outcome and its dynamic change may represent the Wallerian degeneration in motor tracts after hemorrhagic stroke.     

Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas

Triple negative breast cancers (TNBC) are characterized by aggressive tumor biology, lack of targeted treatments and poor prognosis. Anthracyclins were shown to induce immunogenic death in target cells, potentially leading to “endogenous” vaccination. We comparatively assessed expression of cancer testis antigens (CTA) and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors. The study included 83 patients undergoing surgery between January 2003 and December 2009. Tissue sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10, NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL immunophenotype and 48.2% had BL morphology. MAGE-A1 specific staining was most frequently detectable (69.2%), followed by multi-MAGE-A (58%), NY-ESO (27.1%) and MAGE-A10 (16%) specific staining. MAGE-A10 expression significantly correlated with tumor size (p = 0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A specific stainings significantly correlated with advanced clinical stage (p = 0.024, p = 0.041, p = 0.031, respectively). We found no significant association between CTA expression and disease free (DFS) or overall survival (OS). Most interestingly, a significant correlation was observed between expression of MAGE-A10 and NY-ESO and expression of TOPO2A (p = 0.005, p = 0.013). Expression of defined CTA and TOPO2A are significantly correlated in TNBC. Considering the limited therapeutic options for TNBC, these findings might suggest novel forms of combination therapies that should be further explored.