Upregulation of lncRNA DANCR functions as an oncogenic role in non-small lung cancer by regulating miR-214-5p/CIZ1 axis.

OBJECTIVE: Lung cancer has an unfavorable prognosis due to the lack of efficient diagnostic and therapeutic strategies. Therefore, this study sought to figure out the effect of long non-coding RNA (lncRNA) DANCR on lung cancer progression. PATIENTS AND METHODS: LncRNA DANCR and miR-214-5p expressions in non-small cell lung cancer (NSCLC) were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Function assays, including Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were conducted to clarify the role of DANCR and miR-214-5p in the progression of NSCLC. Western blot, Dual-Luciferase reporter assay, and RNA immunoprecipitation assay (RIP) were performed to elucidate the underlying mechanism. RESULTS: LncRNA DANCR was upregulated in NSCLC. The knockdown of lncRNA DANCR inhibited cell proliferation and accelerated cell apoptosis in NSCLC. LncRNA DANCR interacted with miR-214-5p. MiR-214-5p over-expression partially reversed the regulatory effects of DANCR on proliferation and apoptosis in NSCLC. In addition, CIZ1 was the downstream gene binding miR-214-5p. LncRNA DANCR could regulate the miR-214-5p/CIZ1 axis. CONCLUSIONS: Downregulation of lncRNA DANCR inhibited cell proliferation and induced cell apoptosis in NSCLC by regulating the miR-214-5p/CIZ1 axis. LncRNA DANCR may act as an oncogene and promote the progression of NSCLC.

Supracondylar humeral fractures in children: American Academy of Orthopaedic Surgeons appropriate use criteria versus actual management in a teaching hospital.

PURPOSE: The objective of this study was to explore whether there were any differences between the theoretical recommendations for children's supracondylar humeral fractures (CSHF) according to the American Academy of Orthopaedic Surgeons (AAOS) guidelines and the treatments they actually received in our institution. METHODS: We retrospectively reviewed the medical charts and radiographs of all CSHFs at our hospital between January 2015 and December 2018. In all, 301 children meeting our inclusion criteria were identified and evaluated using the AAOS-Appropriate Use Criteria (AUC) application for supracondylar humerus fractures. Actual treatment was then compared with the treatment recommended by the AUC. RESULTS: Actual operative management was undertaken in 0/58 (0%) Gartland type I fractures, 61/108 (56.5%) type II fractures and 98/135 (72.6%) type III fractures. Actual nonoperative management was undertaken in 58/58 (100%) Gartland type I fractures, 47/108 (43.5%) type II fractures and 37/135 (27.4%) type III fractures. Surgeon decisions for nonoperative treatment were in agreement with the AUC recommendations 100% of the time, whereas surgeon decisions for surgery matched the AUC recommendations 65.4% of the time. Predictors of actual operative management were age (p =0.003), fracture classification (p =0.000), associated orthopaedic injury requiring surgery (p =0.025) and anterior humeral line (AHL) not intersecting the capitellum (p =0.008). CONCLUSION: We found low agreement between actual treatments and the AUC-recommended 'appropriate' treatments. The AUC favoured operative intervention more frequently largely on the basis of fracture classification while we emphasized age, fracture classification, associated orthopaedic injury requiring surgery and alignment of the AHL with the capitellum in our operative decision-making process. LEVEL OF EVIDENCE: Therapeutic Level II.

Chondrosarcoma in a paediatric population: a study of 247 cases.

PURPOSE: The aims of present study are to clarify the follow questions: 1) what constitutes paediatric chondrosarcoma?; 2) what are the effects of the demographic and tumour characteristics on survival in patients with paediatric chondrosarcoma?; 3) which prognostic factors of paediatric chondrosarcoma differ from those of the adult population, which have been reported previously? METHODS: Paediatric patients who were diagnosed with chondrosarcoma were searched for using the case listing session protocol of the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 databases (1973 to 2014). The extracted demographic information includes: age, race, gender, year of diagnosis, tumour sites, tumour histological subtype, grade, stage and treatment. RESULTS: A total of 247 paediatric chondrosarcoma patients were extracted and included in our present study. We find that the paediatric patients have significantly better survival rates than the adult patients. The year of diagnosis, tumour sites, tumour histological subtype, grade, stage and surgery received are independent prognostic factors for the survival rate of paediatric chondrosarcoma patients, but race, gender and age are not. CONCLUSION: The paediatric chondrosarcoma patients have better survival rates than the adults. Paediatric patients with a diagnosis at an early age, tumour site at the vertebral column and pelvis/sacrococcyx, myxoid variants, high grade, distant stage and who did not have surgery have a poorer prognosis than patients with a diagnosis at a later age, tumour site at limbs, head and base, chondrosarcoma not otherwise specified, lower grade, localized stage and who received surgery. LEVEL OF EVIDENCE: II -Prognostic Study.

A new family of insect muscarinic acetylcholine receptors.

Most currently used insecticides are neurotoxic chemicals that target a limited number of sites and insect cholinergic neurotransmission is the major target. A potential target for insecticide development is the muscarinic acetylcholine receptor (mAChR), which is a metabotropic G-protein-coupled receptor. Insects have A- and B-type mAChRs and the five mammalian mAChRs are close to the A-type. We isolated a cDNA (CG12796) from the fruit fly, Drosophila melanogaster. After heterologous expression in Chinese hamster ovary K1 cells, CG12796 could be activated by acetylcholine [EC50 (half maximal effective concentration), 73 nM] and the mAChR agonist oxotremorine M (EC50 , 48.2 nM) to increase intracellular Ca(2+) levels. Thus, the new mAChR is coupled to Gq/11 but not Gs and Gi/o . The classical mAChR antagonists atropine and scopolamine N-butylbromide at 100 µM completely blocked the acetylcholine-induced responses. The orthologues of CG12796 can also be found in the genomes of other insects, but not in the genomes of the honeybee or parasitoid wasps. Knockdown of CG12796 in the central nervous system had no effect on male courtship behaviours. We suggest that CG12796 represents the first recognized member of a novel mAChR class.

Involvement of two distinct signalling pathways in IGF-1-mediated central control of hypotensive effects in normotensive and hypertensive rats.

AIMS: Insulin-like growth factor-1 (IGF-1) is abundantly expressed in the nucleus tractus solitarii (NTS). In a previous study, we revealed that the induction of nitric oxide (NO) production in the NTS reduces blood pressure (BP). It is well known that both acute administration and chronic administration of IGF-I reduce BP. The aim of this study was to evaluate the short-term hypotensive effect of IGF-1 in the NTS and to delineate the underlying molecular mechanisms of IGF-1 in the NTS of normotensive WKY rats and spontaneously hypertensive rats (SHRs). METHOD: Microinjections of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the MAP kinase-ERK kinase (MEK) inhibitor PD98059 into the NTS in WKY rats and SHRs were used to study the involvement of IGF-1-induced depressor effects. RESULT: An IGF-1 (7.7 pmol) injection into the NTS resulted in a significant decrease in BP and HR in WKY rats and SHRs. Immunoblotting and immunohistochemical analysis showed that the microinjection of LY294002 (0.6 pmol) or PD98059 (3.0 pmol) into the NTS attenuated the IGF-1-induced depressor effects and Akt or ERK phosphorylation in WKY rats. An attenuation effect of LY294002, but not PD98059, was found in the SHRs. However, the mRNA and protein expression levels of the IGF-1R showed no significant differences in the NTS of the WKY rats and the SHRs. CONCLUSION: These results suggest that distinct Akt and ERK signalling pathways mediated the IGF-1 control of the central depressor effects in WKY rats and SHRs. ERK signalling defects may be associated with the development of hypertension.

AR3 messenger ribonucleic acid expression and its functional implication in human primary testicular failure.

AR3, a major one of androgen receptor (AR) splice variants, has been shown to play a pivotal role in concert with AR signalling in prostate cancer. The present study was undertaken to characterise the expression pattern of AR3 in normal and impaired spermatogenesis. Expression of AR3 mRNA showed significantly lower level in testicular tissues with impaired spermatogenesis when compared to normal tissues. This aberrant expression profile of AR3 in human pathological testes was further confirmed by immunoblotting analysis. Moreover, in situ hybridisation studies revealed that the transcripts of the gene were dominantly localised in the pachytene spermatocytes and round spermatids, suggesting a potential involvement of this transcriptional regulator in the auto-/paracrine regulation of meiotic and post-meiotic differentiation. This hypothesis was strengthened by the observation that AR3 mRNA expression was positively correlated to average seminiferous tubule score and was negatively correlated to serum FSH level. To the best of our knowledge, such a distinct expression profile of AR3 has not been reported previously in human testis. Overall, our data are suggestive of a novel site of action of AR3 during human spermatogenesis and should shed light on the complicated circuit composed of AR and its splice variants.

Extracorporeal membrane oxygenation as treatment for acute respiratory failure and subsequent pneumothorax caused by Pneumocystis jirovecii pneumonia in a kidney transplant recipient.

Acute respiratory failure (ARF) accompanied by pneumothorax caused by Pneumocystis jirovecii pneumonia (PJP) is often fatal. We present our experience using extracorporeal membrane oxygenation as treatment for ARF and subsequent pneumothorax caused by PJP in a kidney transplant recipient.

Genetic variants on 17q21 are associated with asthma in a Han Chinese population.

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.

Polymorphisms in the DNA repair gene XRCC1 and associations with systemic lupus erythematosus risk in the Taiwanese Han Chinese population.

XRCC1 plays a central role in mammalian DNA repair processes. Two polymorphisms of XRCC1, rs1799782 (Arg > Trp at codon 194) and rs25487 (Arg > Gln at codon 399), are common in the Han Chinese population. Our objective was to analyze the relationship between these two functional single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in the Taiwanese Han Chinese population. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on 172 SLE patients and 160 normal controls. Our data indicate that the frequency of A/G at codon 399 differed between patients and controls (p = 0.01; odds ratio: 1.80; 95% confidence interval: 1.17-2.75), but the allelic frequency analysis did not reveal significant differences. For the SNP at codon 194, there were no differences in either allelic or genotype frequencies between SLE patients and normal subjects. Clinical association studies of SLE symptoms revealed the involvement of the A/G polymorphism at codon 399 in SLE pathogenesis. Our results indicate that a functional SNP at codon 399 of XRCC1 is associated with the development of SLE.

Venlafaxine vs. paroxetine in the acute phase of treatment for major depressive disorder among Han Chinese population in Taiwan.

PURPOSE: Clinical studies have suggested that venlafaxine induces a higher remission rate than paroxetine. However, very few studies have evaluated relapse episodes over treatment periods longer than a few weeks, and the cut-off score of 7 on the Hamilton Rating Scale for Depression (HRSD) often used to define remission is too high. This score is associated with the high rates of social function impairment. We report on a single centre, open-label, prospective 24-week study to investigate the comparative efficacy of acute treatments with venlafaxine and paroxetine, using different definitions of response and remission rates. METHODS: Outpatients satisfying DSM-IV criteria for major depression with a baseline HRSD17 score of at least 16 were eligible. Following baseline evaluations, the patients were assigned to receive venlafaxine 75-225 mg/day with the mean dosage 141.35 +/- 26.98 (SD) mg/day (n = 78), or paroxetine 20 mg/day (n = 92) for 24 weeks. Efficacy was assessed using the mean change in HRSD(17) score from baseline, the response rate and the remission rates based on different criteria for remission (HRSD(17) score < or = 7 or 5). RESULTS: One hundred and seventy patients were evaluated for efficacy; 78 treated with venlafaxine and 92 with paroxetine. Over the treatment period, venlafaxine was comparable with paroxetine on most outcome measures, whereas paroxetine produced significantly higher remission rates at weeks 4, 8, 16, 20 and 24 weeks when the lower cutoff of 5 was used. CONCLUSIONS: Venlafaxine treatment was similar to paroxetine according to the typical efficacy measures for treating outpatients with major depression. However, based on the stricter remission criterion, paroxetine might be superior to venlafaxine.

Optically heterodyne diagnosis of a high-saturation-power undoped InP sandwiched InGaAs p-i-n photodiode grown on GaAs.

We demonstrate the optical heterodyne diagnostics and high saturation power characteristics of a novel undoped InP sandwiched In(0.53)Ga(0.47)As p-i-n photodiode with a partially p-doped photoabsorption layer, which is grown on a linearly graded metamorphic In(x)Ga(1-x)P buffered GaAs substrate layer and exhibits an excellent low dark current density of 3.6x10(-7) A/cm(2). Such a top-illuminated optical receiver exhibits an illuminating window of 60-mum diameter, which performs ultra-linear power handling capability up to 18 dBm at 1550 nm, providing a maximum photocurrent of 35 mA under a reverse bias of 9 volts. These result in extremely high current bandwidth and bandwidth-responsivity products of 350 mA*GHz and 4.8 GHz*A/W, respectively, at receiving frequency of up to 10 GHz.

Malignant phyllodes tumor of the prostate.

This is a report of a 70-year-old man with malignant phyllodes tumor of prostate. The retropubic prostatectomy was done. The stroma of the tumor was cellular and composed of elongated cells with spindle shaped nuclei and fragmented bizarre giant cells. After recovery from surgery, prophylatic radiotherapy was given over 2 months. A case report of a patient treated at our medical center and a review of the literature was done.

Effect of heterogeneity in fracture permeability on the potential for liquid seepage into a heated emplacement drift of the potential repository.

A numerical model was used to investigate the effect of spatial variability in fracture permeability on liquid seepage and moisture distribution in the vicinity of a waste emplacement drift in the unsaturated zone (UZ) of Yucca Mountain. The model is based on a two-dimensional, cross-sectional, dual-permeability model of the unsaturated zone at Yucca Mountain and uses a stochastic approach to investigate the effect of small-scale heterogeneous features. The studies were conducted using one uniform fracture permeability case, three realizations of stochastically generated fracture permeability, one discrete permeability feature case, and one increased ambient liquid flux case. In all cases, the models predict that completely dry drift conditions will develop above and below the drift in 10-100 years and remain dry for 1000-2000 years. During this period, the models predict no seepage into drifts, although liquid flux above the drifts and within the drift pillars may increase by up to two orders of magnitude above ambient flux. This is because the heat released by the emplaced waste is sufficient to vaporize liquid flux of one to two orders of magnitude higher than present-day ambient flux for over 1000 years. The results also show that unsaturated zone thermal-hydrological (TH) models with uniform layer permeability can adequately predict the evolution of seepage and moisture distribution in the rock mass surrounding the repository drifts. The models further show that although variability in fracture permeability may focus and enhance liquid flow in regions of enhanced liquid saturation (due to condensation above the drifts), vaporization and vapor diffusion can maintain a dry environment within the drifts for thousands of years.

Preliminary 3-D site-scale studies of radioactive colloid transport in the unsaturated zone at Yucca Mountain, Nevada.

The U.S. Department of Energy (DOE) is actively investigating the technical feasibility of permanent disposal of high-level nuclear waste in a repository to be situated in the unsaturated zone (UZ) at Yucca Mountain (YM), Nevada. In this study we investigate, by means of numerical simulation, the transport of radioactive colloids under ambient conditions from the potential repository horizon to the water table. The site hydrology and the effects of the spatial distribution of hydraulic and transport properties in the Yucca Mountain subsurface are considered. The study of migration and retardation of colloids accounts for the complex processes in the unsaturated zone of Yucca Mountain, and includes advection, diffusion, hydrodynamic dispersion, kinetic colloid filtration, colloid straining, and radioactive decay. The results of the study indicate that the most important factors affecting colloid transport are the subsurface geology and site hydrology, i.e., the presence of faults (they dominate and control transport), fractures (the main migration pathways), and the relative distribution of zeolitic and vitric tuffs. The transport of colloids is strongly influenced by their size (as it affects diffusion into the matrix, straining at hydrogeologic unit interfaces, and transport velocity) and by the parameters of the kinetic-filtration model used for the simulations. Arrival times at the water table decrease with an increasing colloid size because of smaller diffusion, increased straining, and higher transport velocities. The importance of diffusion as a retardation mechanism increases with a decreasing colloid size, but appears to be minimal in large colloids.

Holography and noncommutative yang-mills theory

In this Letter a recently proposed gravity dual of noncommutative Yang-Mills theory is derived from the relations between closed string moduli and open string moduli recently suggested by Seiberg and Witten. The only new input one needs is a simple form of the running string tension as a function of energy. This derivation provides convincing evidence that string theory integrates with the holographical principle and demonstrates a direct link between noncommutative Yang-Mills theory and holography.

A fluorescence detection scheme for capillary electrophoresis of N-methylcarbamates with on-column thermal decomposition and derivatization

This paper describes a fluorescence detection method for N-methylcarbamate (NMC) pesticides in micellar electrokinetic chromatography (MEKC) separation. Fulfillment of the fluorescence detection hinged on the discovery that quaternary ammonium surfactants (particularly cetyltrimethylammonium bromide, CTAB), besides serving as hydrophobic pseudophases in MEKC, are also capable of catalyzing the thermal decomposition of NMCs to liberate methylamine. Thus, a multifunctional MEKC medium consisting of borate buffer, CTAB, and derivatizing components (o-phthaldialdehyde/2-mercaptoethanol) was formulated, which allowed first normal MEKC separation, subsequent thermal decomposition, and finally in situ derivatization of NMCs. With careful optimization of the operation conditions, fluorescence detection of 10 NMC compounds was achieved, with column efficiencies typically higher than 50,000 and detection limits better than 0.5 ppm. The present work represents an unprecedented effort in capillary electrophoresis (CE), in which an intact capillary was consecutively utilized as chambers for separation, decomposition, derivatization, and detection, without involving any interfacing features. The success in the implementation of such a detection system resulted in strikingly simple instrumentation as compared with the traditional postcolumn fluorescence determination of NMCs by reversed-phase HPLC. Similar protocols should be workable in the determination of a wide range of pesticides and pharmaceuticals in CE formats.