喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。     

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection

PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (&amp;gt; 30 days) outcomes after intervention.ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA &amp;lt; 25% in 1 cardiac cycle (P&amp;nbsp;= .049) and larger D-TLA (P &amp;lt; .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA &amp;gt; 21.5% group compared with the D-TLA ≤ 21.5% group (all P &amp;lt; .001).ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.     

miR-451a suppresses the development of breast cancer via targeted inhibition of CCND2

Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan‒Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment.     

Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study

IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P&amp;nbsp;&amp;lt; .001 and P&amp;nbsp;=&amp;nbsp;.0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P&amp;nbsp;&amp;lt; .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P&amp;nbsp;&amp;lt; .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P&amp;nbsp;&amp;lt; .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P&amp;nbsp;&amp;lt; .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.     

Riesgo de recurrencia tras retirada de la anticoagulación en pacientes con enfermedad tromboembólica venosa no provocada: validación externa del nomograma de Viena y del modelo predictivo DASH

IntroductionScales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months.MethodsThis was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration).ResultsOf 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p &amp;lt;.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p &amp;lt;.05).ConclusionsOur study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).     

Infección por el virus de la hepatitis C y nuevas estrategias de tratamiento

Hepatitis C is a major public health problem worldwide. This disease is caused by the hepatitis C virus, which is characterised by its genetic diversity. The infection is usually asymptomatic. However, between 60% and 80% of HCV-infected individuals will progress to chronic hepatitis, 20% to liver cirrhosis in the medium-to long-term and, each year, between 1% and 4% of these patients with cirrhosis will develop hepatocellular carcinoma (HCC). A Spanish consensus document has recently been drafted to diagnose hepatitis C in a single step, consisting of active investigation (antibodies and viremia) in a single sample, which according to the experts, would reduce the time to access treatment and avoid tracking losses. To definitively change the hepatitis C treatment paradigm, direct-acting antiviral drugs (DAAs) have been approved, whose development has been based on achieving cure rates close to 100% regardless of the genotype of the virus, ie, pangenotypes, with good tolerance and bioavailability. These drugs have constituted a real therapeutic revolution. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016», which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A.© 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

负载IL-4及BMP-2的氧化石墨烯-羧甲基壳聚糖凝胶对骨免疫和骨修复的早期影响研究

&amp;#x076ee;&amp;#x07684;&amp;#x063a2;&amp;#x08ba8;&amp;#x08d1f;&amp;#x08f7d; IL-4 &amp;#x0548c; BMP-2 &amp;#x07684;&amp;#x06c27;&amp;#x05316;&amp;#x077f3;&amp;#x058a8;&amp;#x070ef;&amp;#x0ff08;graphene oxide&amp;#x0ff0c;GO&amp;#x0ff09;-&amp;#x07fa7;&amp;#x07532;&amp;#x057fa;&amp;#x058f3;&amp;#x0805a;&amp;#x07cd6;&amp;#x0ff08;carboxymethyl chitosan&amp;#x0ff0c;CMC&amp;#x0ff09;&amp;#x051dd;&amp;#x080f6;&amp;#x08bf1;&amp;#x05bfc;&amp;#x05de8;&amp;#x0566c;&amp;#x07ec6;&amp;#x080de; M2 &amp;#x0578b;&amp;#x05206;&amp;#x05316;&amp;#x053ca;&amp;#x05bf9; BMSCs &amp;#x06210;&amp;#x09aa8;&amp;#x05206;&amp;#x05316;&amp;#x07684;&amp;#x05f71;&amp;#x054cd;&amp;#x03002;&amp;#x065b9;&amp;#x06cd5;&amp;#x053d6; CMC&amp;#x03001;GO &amp;#x05236;&amp;#x05907;&amp;#x06df7;&amp;#x05408;&amp;#x06eb6;&amp;#x06db2;&amp;#x0540e;&amp;#x0ff0c;&amp;#x05206;&amp;#x0522b;&amp;#x06dfb;&amp;#x052a0; PBS&amp;#x03001;IL-4&amp;#x03001;BMP-2 &amp;#x06216; IL-4+BMP-2&amp;#x0ff0c;&amp;#x05728;&amp;#x04ea4;&amp;#x08054;&amp;#x05242;&amp;#x04f5c;&amp;#x07528;&amp;#x04e0b;&amp;#x05236;&amp;#x05907;&amp;#x05355;&amp;#x07eaf;&amp;#x06216;&amp;#x08d1f;&amp;#x08f7d;&amp;#x04e0d;&amp;#x0540c;&amp;#x056e0;&amp;#x05b50;&amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x0652f;&amp;#x067b6;&amp;#x0ff1b;&amp;#x053d6;&amp;#x05355;&amp;#x07eaf; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x08868;&amp;#x05f81;&amp;#x089c2;&amp;#x06d4b;&amp;#x0ff0c;&amp;#x05305;&amp;#x062ec;&amp;#x05927;&amp;#x04f53;&amp;#x03001;&amp;#x0626b;&amp;#x063cf;&amp;#x07535;&amp;#x0955c;&amp;#x053ca;&amp;#x05085;&amp;#x091cc;&amp;#x053f6;&amp;#x053d8;&amp;#x06362;&amp;#x07ea2;&amp;#x05916;&amp;#x05438;&amp;#x06536;&amp;#x05149;&amp;#x08c31;&amp;#x04eea;&amp;#x0ff08;Fourier transform infrared spectroscopy&amp;#x0ff0c;FTIR&amp;#x0ff09;&amp;#x068c0;&amp;#x06d4b;&amp;#x0ff0c;&amp;#x04ee5;&amp;#x05355;&amp;#x07eaf; CMC &amp;#x051dd;&amp;#x080f6;&amp;#x04f5c;&amp;#x04e3a;&amp;#x05bf9;&amp;#x07167;&amp;#x0ff1b;&amp;#x053d6;&amp;#x08d1f;&amp;#x08f7d;&amp;#x04e0d;&amp;#x0540c;&amp;#x056e0;&amp;#x05b50;&amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x0884c;&amp;#x04f53;&amp;#x05916;&amp;#x07f13;&amp;#x091ca;&amp;#x05b9e;&amp;#x09a8c;&amp;#x03002;&amp;#x053d6; 4&amp;#x0ff5e;5 &amp;#x05468;&amp;#x09f84; SPF &amp;#x07ea7; SD &amp;#x096cc;&amp;#x06027;&amp;#x05927;&amp;#x09f20;&amp;#x05206;&amp;#x079bb;&amp;#x057f9;&amp;#x0517b;&amp;#x05de8;&amp;#x0566c;&amp;#x07ec6;&amp;#x080de;&amp;#x0ff0c;&amp;#x05206;&amp;#x0522b;&amp;#x04e0e;&amp;#x05355;&amp;#x07eaf;&amp;#x04ee5;&amp;#x053ca;&amp;#x08d1f;&amp;#x08f7d;&amp;#x04e0d;&amp;#x0540c;&amp;#x056e0;&amp;#x05b50;&amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x057f9;&amp;#x0517b;&amp;#x0ff0c;24 h &amp;#x0540e;&amp;#x0884c; CD206 &amp;#x0514d;&amp;#x075ab;&amp;#x08367;&amp;#x05149;&amp;#x068c0;&amp;#x06d4b;&amp;#x05de8;&amp;#x0566c;&amp;#x07ec6;&amp;#x080de;&amp;#x05206;&amp;#x05316;&amp;#x060c5;&amp;#x051b5;&amp;#x0ff1b;&amp;#x053d6;&amp;#x07b2c; 3 &amp;#x04ee3;&amp;#x05927;&amp;#x09f20; BMSCs &amp;#x05206;&amp;#x0522b;&amp;#x04e0e;&amp;#x05355;&amp;#x07eaf;&amp;#x04ee5;&amp;#x053ca;&amp;#x08d1f;&amp;#x08f7d;&amp;#x04e0d;&amp;#x0540c;&amp;#x056e0;&amp;#x05b50;&amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x06210;&amp;#x09aa8;&amp;#x08bf1;&amp;#x05bfc;&amp;#x057f9;&amp;#x0517b;&amp;#x0ff0c;10 d &amp;#x0540e;&amp;#x0884c; ALP &amp;#x067d3;&amp;#x08272;&amp;#x089c2;&amp;#x06d4b;&amp;#x065e9;&amp;#x0671f;&amp;#x06210;&amp;#x09aa8;&amp;#x0ff0c;21 d &amp;#x0884c;&amp;#x0831c;&amp;#x07d20;&amp;#x07ea2;&amp;#x067d3;&amp;#x08272;&amp;#x089c2;&amp;#x06d4b;&amp;#x0665a;&amp;#x0671f;&amp;#x06210;&amp;#x09aa8;&amp;#x03002;&amp;#x07ed3;&amp;#x0679c;&amp;#x05927;&amp;#x04f53;&amp;#x089c2;&amp;#x05bdf; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x05448;&amp;#x068d5;&amp;#x08272;&amp;#x03001;&amp;#x0534a;&amp;#x0900f;&amp;#x0660e;&amp;#x072b6;&amp;#x0ff1b;&amp;#x0626b;&amp;#x063cf;&amp;#x07535;&amp;#x0955c;&amp;#x089c2;&amp;#x05bdf;&amp;#x0793a;&amp;#x0ff0c;GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x05b54;&amp;#x05f84;&amp;#x053ca;&amp;#x05b54;&amp;#x058c1;&amp;#x0539a;&amp;#x05ea6;&amp;#x04e0e;&amp;#x05355;&amp;#x07eaf; CMC &amp;#x051dd;&amp;#x080f6;&amp;#x076f8;&amp;#x04f3c;&amp;#x0ff0c;&amp;#x04f46;&amp;#x05185;&amp;#x058c1;&amp;#x07c97;&amp;#x07cd9;&amp;#x05ea6;&amp;#x0589e;&amp;#x052a0;&amp;#x0ff1b;FTIR &amp;#x068c0;&amp;#x06d4b;&amp;#x0663e;&amp;#x0793a; CMC &amp;#x053d1;&amp;#x0751f;&amp;#x0805a;&amp;#x05408;&amp;#x05f62;&amp;#x06210;&amp;#x051dd;&amp;#x080f6;&amp;#x03002;&amp;#x04f53;&amp;#x05916;&amp;#x07f13;&amp;#x091ca;&amp;#x05b9e;&amp;#x09a8c;&amp;#x0793a; 3 &amp;#x079cd;&amp;#x08d1f;&amp;#x08f7d;&amp;#x04e0d;&amp;#x0540c;&amp;#x056e0;&amp;#x05b50;&amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x07f13;&amp;#x091ca;&amp;#x06027;&amp;#x080fd;&amp;#x076f8;&amp;#x04f3c;&amp;#x0ff0c;&amp;#x05747;&amp;#x05448;&amp;#x07ebf;&amp;#x06027;&amp;#x07f13;&amp;#x06162;&amp;#x091ca;&amp;#x0653e;&amp;#x056e0;&amp;#x05b50;&amp;#x03002;CD206 &amp;#x0514d;&amp;#x075ab;&amp;#x08367;&amp;#x05149;&amp;#x068c0;&amp;#x06d4b;&amp;#x0793a; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x053ef;&amp;#x08bf1;&amp;#x05bfc;&amp;#x05de8;&amp;#x0566c;&amp;#x07ec6;&amp;#x080de; M2 &amp;#x0578b;&amp;#x05206;&amp;#x05316;&amp;#x0ff0c;ALP &amp;#x053ca;&amp;#x0831c;&amp;#x07d20;&amp;#x07ea2;&amp;#x067d3;&amp;#x08272;&amp;#x0793a; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x053ef;&amp;#x08bf1;&amp;#x05bfc; BMSCs &amp;#x06210;&amp;#x09aa8;&amp;#x05206;&amp;#x05316;&amp;#x0ff1b;&amp;#x05176;&amp;#x04e2d;&amp;#x08d1f;&amp;#x08f7d; IL-4+BMP-2 &amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x04f5c;&amp;#x07528;&amp;#x06700;&amp;#x0663e;&amp;#x08457;&amp;#x0ff08;P&amp;#x0003c;0.05&amp;#x0ff09;&amp;#x03002; &amp;#x07ed3;&amp;#x08bba;&amp;#x08d1f;&amp;#x08f7d; IL-4 &amp;#x0548c; BMP-2 &amp;#x07684; GO-CMC &amp;#x051dd;&amp;#x080f6;&amp;#x053ef;&amp;#x08bf1;&amp;#x05bfc;&amp;#x05de8;&amp;#x0566c;&amp;#x07ec6;&amp;#x080de; M2 &amp;#x0578b;&amp;#x05206;&amp;#x05316;&amp;#x0ff0c;&amp;#x0589e;&amp;#x05f3a; BMSCs &amp;#x06210;&amp;#x09aa8;&amp;#x05206;&amp;#x05316;&amp;#x080fd;&amp;#x0529b;&amp;#x0ff0c;&amp;#x04e3a;&amp;#x0540e;&amp;#x0671f;&amp;#x09aa8;&amp;#x07f3a;&amp;#x0635f;&amp;#x04fee;&amp;#x0590d;&amp;#x053ca;&amp;#x09aa8;&amp;#x0514d;&amp;#x075ab;&amp;#x08c03;&amp;#x08282;&amp;#x07814;&amp;#x07a76;&amp;#x063d0;&amp;#x04f9b;&amp;#x04e86;&amp;#x065b0;&amp;#x07684;&amp;#x07b56;&amp;#x07565;&amp;#x03002;     

Evolución e impacto bibliométrico de las becas de la Sociedad Española de Cardiología/Fundación Española del Corazón en el periodo 2007-2012

Introduction and objectivesThe Spanish Society of Cardiology/Spanish Heart Foundation (SEC/FEC) annually awards grants for cardiovascular research projects. Our objective was to analyze the trend in these investments and their resulting scientific production from 2007 to 2012.MethodsA search of the publications funded by the SEC/FEC was carried out, according to the following inclusion criteria: publication in a journal indexed in MEDLINE or EMBASE, publication date after the grant, authorship by the principal investigator of the grant, and acknowledgment of SEC/FEC funding. The impact factor and subsequent citations of the articles were analyzed (Web of Science).ResultsA total of 235 grants were awarded (39/y) with an allocation of €3 854 300 (€642 383/y), 37% of them to women. In all, 122 publications resulted from 88 research projects (37%) funded by the SEC/FEC. Up to October 2017, these publications had received 2258 citations in subsequent studies in the Web of Science, with a mean of 18.5 and a median of 8 citations/study.ConclusionsDespite the economic crisis, the mean number and size of the grants awarded by the SEC/FEC increased in the period analyzed. Grants were awarded on an equal opportunity basis to men and women. The bibliometric impact of the funded projects is acceptable, although efforts should be made to improve it.