Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) rs10845498 Polymorphism Is Associated with a Decreased Risk of Non-Small Cell Lung Cancer

Objectives: Low-density lipoprotein receptor-related protein 6 (LRP6) modulates Wnt signaling transduction. Altered LRP6 expression leads to abnormal Wnt protein activation, cell proliferation and tumorigenesis. This study investigated the association between LRP6 single-nucleotide polymorphisms (SNPs) and non-small-cell lung cancer (NSCLC) in a Chinese population. Methods: A total of 500 NSCLC patients and 500 healthy controls were recruited for assessment of four LRP6 SNPs using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Results: The frequency of the LRP6 rs10845498 genotype was 60.9% (A/A), 35.5% (AG) and 3.6% (GG) in patients with lung squamous cell carcinoma (SCC) and 69.2% (A/A), 27.2% (A/G) and 3.6% (GG) in controls. Logistic regression analysis revealed that the LRP6 rs10845498 A/A major allele was associated with a reduced risk in developing lung SCC (OR = 0.69; 95% CI, 0.48-1.00; P=0.04), and tobacco smokers had a 2.21 fold greater risk in developing SCC than nonsmokers (p<0.01, 95% CI, 1.72-2.85), and tobacco smokers who carried an “A” allele (AA+AG) in rs6488507 had a 2.34-fold greater risk in developing NSCLC than other patients (p< 0.01, 95%CI, 1.74-3.13). Conclusions: The LRP6 rs10845498 SNP is associated with a reduced risk of lung SCC, while tobacco smoke increases the risk. LRP6 rs6488507 polymorphism synergistically increased the risk of NSCLC in tobacco smokers. Further studies are needed to elucidate the functional impact of LRP6 expression and activity in NSCLC.     

Surgical treatment of jaw osteonecrosis in “Krokodil” drug addicted patients

Retrospective study of jaw osteonecrosis treatment in patients using the “Krokodil” drug from 2009 to 2013.On the territory of the former USSR countries there is widespread use of a self-produced drug called “Krokodil”. Codeine containing analgesics (“Sedalgin”, “Pentalgin” etc), red phosphorus (from match boxes) and other easily acquired chemical components are used for synthesis of this drug, which used intravenously. Jaw osteonecrosis develops as a complication in patients who use “Krokodil”. The main feature of this disease is jawbone exposure in the oral cavity. Surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”.40 “Krokodil” drug addict patients with jaw osteonecrosis were treated. Involvement of maxilla was found in 11 patients (27.5%), mandible in 21 (52.5%), both jaws in 8 (20%) patients. 35 Lesions were found in 29 mandibles and 21 lesions in 19 maxillas. Main factors of treatment success are: cessation of “Krokodil” use in the pre- (minimum 1 month) and postoperative period and osteonecrosis area resection of a minimum of 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues. Surgery was not delayed until sequestrum formation. In the mandible marginal or segmental resection (with or without TMJ exarticulation) was performed. After surgery recurrence of disease was seen in 8 (23%) cases in the mandible, with no cases of recurrence in the maxilla.According to our experience in this case series, surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”. Cessation of drug use and jaw resection minimize the rate of recurrences in such patients.     

Plasma hydrogenated cationic detonation nanodiamonds efficiently deliver to human cells in culture functional siRNA targeting the Ewing sarcoma junction oncogene

The expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, particularly in urine, which is impossible for 35 nm particles. Here, we report that hydrogenated cationic nanodiamonds of primary size 7 nm (ND-H) have also a high affinity for siRNA and are capable of delivering them in cells. With siRNA/ND-H complexes, we measured a high inhibition efficacy of EWS/FLI-1 gene expression in Ewing sarcoma cell line. Electron microscopy investigations showed ND-H in endocytosis compartments, and especially in macropinosomes from which they can escape before siRNA degradation occurred. In addition, the association of EWS/FLI-1 silencing by the siRNA/ND-H complex with a vincristine treatment yielded a potentiation of the toxic effect of this chemotherapeutic drug. Therefore ND-H appears as a promising delivery agent in anti-tumoral gene therapy.     

硝苯地平与硫酸镁联用治疗妊娠期高血压疾病的分析

目的：探讨硝苯地平联合硫酸镁用于妊娠期高血压疾病治疗的临床效果。方法将我院收治的妊娠期高血压疾病患者96例随机分成观察组48例（硝苯地平联合硫酸镁治疗）和对照组48例（硫酸镁治疗），对比2组的治疗效果。结果2组治疗有效率相比差异具有显著性（P<0.05）。结论硫酸镁和硝苯地平联合治疗能够在改善患者心肌血氧的同时保护心肌功能，避免并发症的出现，减少高血压发病率，保障孕妇和婴儿的生命健康。     

Development of Research Agenda in Prostate Artery Embolization: Summary of Society of Interventional Radiology Consensus Panel

PurposeTo summarize the Society of Interventional Radiology Foundation’s Research Consensus Panel development of a research agenda on prostate artery embolization (PAE).Materials and MethodsPAE for the treatment of lower urinary tract symptoms has been shown to be safe and effective in decreasing symptoms and prostate size. Lack of randomized controlled trials (RCTs) on PAE in the United States has prevented inclusion in American Urologic Association guideline recommendations for treatment of lower urinary tract symptoms resulting from benign prostatic hyperplasia. Recognizing the need for well-designed trials, the SIR Foundation funded a Research Consensus Panel to prioritize a research agenda. The panel included interventional radiologists, urologists, SIR Foundation leadership, and industry representatives. The goal of the meeting was to discuss weaknesses with current data and study design for development of US trials to report long-term outcomes data.ResultsFinal consensus on a research design could not be made because the group was split on 3 research designs: (i) RCT of PAE versus sham with crossover of the sham group. (ii) RCT of PAE versus simple prostatectomy. (iii) RCT of PAE versus holmium laser enucleation of the prostate/thulium laser enucleation of the prostate. The panel recommended a nonindustry-funded registry to obtain real-world data.ConclusionsLevel 1 data are required to be included in the American Urologic Association guidelines for treatment of benign prostatic hyperplasia. Because of concerns with all 3 study designs, the panel did not reach a consensus. Further meetings are planned with the panel to select among these research designs.