接受选择性淋巴结照射的食管鳞癌患者预后和失败模式的分析

目的探讨接受选择性淋巴结照射(ENI)的食管鳞癌患者预后和失败模式。方法回顾性分析2005年1月至2012年12月河北医科大学第四医院收治的179例符合入组条件的食管鳞癌患者,分析肿瘤局部相关因素预测患者预后的价值,分析影响患者近期疗效、预后的影响因素,并对影响患者总生存率(OS)、无进展生存率(PFS)和复发的指标分别进行单因素和多因素分析。结果全组患者1、3、5年OS和PFS分别为77.1%、40.1%、26.0%和62.6%、30.6%、20.3%。多因素分析结果显示声音嘶哑、cN分期、cTNM分期、GTV-横径(GTV-D)和GTV-体积/长度(GTV-V/L)为影响患者OS的独立性影响因素(P<0.05);声音嘶哑、cTNM分期和近期疗效为影响患者PFS的独立性影响因素(P<0.05)。全组有75例(41.9%)患者出现复发,61例(34.1%)远处转移,其中19例(10.6%)为合并复发和远处转移。75例复发患者中64例(85.3%)患者为单纯食管复发,4例(5.3%)为单纯淋巴结复发,另7例(9.3%)患者为食管合并淋巴结复发。治疗后达完全缓解(CR)的63例患者中有18例患者出现复发,其中仅有2例患者出现淋巴结复发;logistic多因素分析结果显示患者周边组织/器官受侵、GTV-D和近期疗效为影响患者复发的独立性影响因素(P<0.05)。结论食管鳞癌患者接受ENI确实可行,其失败主要模式仍为食管复发;治疗前声音嘶哑、GTV-D和GTV-V/L较大、临床分期较晚和近期疗效不佳为患者预后较差的指标;肿瘤周边组织受侵、GTV-D和近期疗效是影响患者失败的独立性因素。     

Cutaneous nociception: Role of keratinocytes

Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.     

Oral Dispersible System: A New Approach in Drug Delivery System

Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day''s more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form.     

Respecting the circle of life: one year outcomes from a randomized controlled comparison of an HIV risk reduction intervention for American Indian adolescents

Potential for widespread transmission of HIV/AIDS among American Indian (AI) adolescents exists, yet no evidence-based interventions (EBIs) have been adapted and evaluated with this population. Intensive psychoeducation may improve knowledge and decision-making which could potentially translate to reductions in HIV risk behaviors. A peer group randomized controlled comparison of an adapted EBI vs. control was delivered over an eight-day summer basketball camp in one reservation-based tribal community to adolescents ages 13–19. Outcome data were gathered immediately post-camp and at 6 and 12 months follow-up. Self-selected peer groups were randomized to intervention (n = 138) or control (n = 129) conditions for a total sample of 267 participants (56.2% female), mean age 15.1 years (SD = 1.7). Intervention participants had better condom use self-efficacy post-camp (Adjusted Mean Difference [AMD] = ?0.75, p < 0.005) and at 6 (AMD = ?0.44, p < 0.005) and 12 months (AMD = ?0.23, p < 0.05) follow-up. Intervention participants also had higher HIV prevention and transmission knowledge (post-camp: AMD = 0.07, p < 0.01; 6 months: AMD = 0.06, p < 0.01) were more likely to believe condoms prevent sexually transmitted infections (post-camp: RR = 1.41, p < 0.005; 6 months: RR = 1.34, p < 0.05), to talk with an adult about HIV/AIDS (post-camp: RR=1.78, p < 0.005; 6 months: RR = 1.14, p < 0.005), had higher partner negotiation efficacy related to substance use during sex (post-camp: AMD = 0.37, p < 0.01), and were more likely to intend to use a condom (post-camp: RR = 1.39, p < 0.01). The adapted intervention had short- and medium-term impacts on AI adolescent risk for HIV/AIDS, but attenuated at 12 months. Intervention delivery through a community-based camp is feasible and acceptable with strong retention. Additional study is needed to evaluate the adapted intervention's impact on sexual risk behaviors and if booster sessions and parent involvement translate to long-term impacts.     

Atypical Abnormal Pulmonary Vein Drainage with Atrial Septal Defect: Surgical Treatment

Sinus venosus atrial septal defect (SV‐ASD) usually coexists with partial anomalous pulmonary vein connection (PAPVC). It is a difficult diagnosis in transthoracic echocardiography (TTE) due to eccentric position of defects. We present a rare case of atypical anatomical variation in PAPVC, which was never described before. Two right pulmonary veins drained into superior vena cava, which overrode SV‐ASD and interatrial septum, a third pulmonary vein into the right atrium. Complete diagnosis could not be set after TTE, nor transesophageal echocardiography, whereas angio‐CT was finally conclusive. This diagnostic approach allowed the surgical planning.     

Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.     

AuNP flares-capped mesoporous silica nanoplatform for MTH1 detection and inhibition

The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a vulnerability factor and an attractive target for anticancer therapy. However, there is currently a lack of selective and effective platforms for the detection and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN) nanoplatform that is capable of detecting MTH1 mRNA and simultaneously suppressing MTH1 activity. The AuNP flares are made from AuNPs that are functionalized with a dense shell of MTH1 recognition sequences hybridized to short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces the opening of the pores and the release of S-crizotinib in an mRNA-dependent manner, leading to significant cytotoxicity in cancer cells and improved therapeutic response in mouse xenograft models. We anticipate that this nanoplatform may be an important step toward the development of MTH1-targeting theranostics and also be a useful tool for cancer phenotypic lethal anticancer therapy.     

Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio

BackgroundDual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI).ObjectiveThe present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI).MethodsWe designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant.ResultsCompared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05).ConclusionTAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.