LncRNA LINP1 promotes malignant progression of pancreatic cancer by adsorbing microRNA-491-3p.

OBJECTIVE: The purpose of this study was to explore the mechanism by which long noncoding RNA (lncRNA) LINP1 promoted the development of pancreatic cancer (PCa). Meanwhile, the regulatory relationship between lncRNA LINP1 and microRNA-491-3p was further investigated to provide an effective theoretical basis for the treatment of this cancer. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to examine lncRNA LINP1 and microRNA-491-3p expression in tumor tissue specimens collected from 56 PCa patients, and the interplay between lncRNA LINP1 expression and some clinical indicators, as well as prognosis of patients with PCa was also analyzed. Meanwhile, in vitro, qRT-PCR further verified lncRNA LINP1 level in PCa cell lines. In addition, lncRNA LINP1 knockdown model was constructed using lentivirus in PCa cell lines CFPAC-1 and BxPC-3, and Cell Counting Kit-8 (CCK-8), transwell, and cell wound healing assays were carried out to evaluate the impact of lncRNA LINP1 on the function of PCa cells. Finally, Dual-Luciferase reporting assay and cell reverse experiments were applied to uncover the potential mechanism. RESULTS: QRT-PCR revealed that lncRNA LINP1 showed a significantly higher expression in pancreatic tumor tissue samples than in adjacent normal ones. Compared with patients with low expression of lncRNA LINP1, patients with highly expressed lncRNA LINP1 showed a higher incidence of distant metastasis, but a lower overall survival rate. In addition, compared to the sh-NC group, the proliferation, invasion, and migration ability of PCa cells decreased remarkably in LINP1 knockdown group. The results of Luciferase reporting assay demonstrated that lncRNA LINP1 could be targeted by microRNA-491-3p through a specific binding site, and qRT-PCR results uncovered a negative correlation between microRNA-491-3p and lncRNA LINP1 expression in PCa tissues. Finally, the recovery experiment revealed a mutual regulation between LINP1 and microRNA-491-3p, which may jointly regulate the malignant progression of PCa. CONCLUSIONS: LncRNA LINP1 is able to enhance the proliferation and metastasis of PCa cells by modulating microRNA-491-3p, thus affecting the incidence of lymph node or distant metastasis and prognosis of patients with PCa.

Scale law of complex deformation transitions of nanotwins in stainless steel.

Understanding the deformation behavior of metallic materials containing nanotwins (NTs), which can enhance both strength and ductility, is useful for tailoring microstructures at the micro- and nano- scale to enhance mechanical properties. Here, we construct a clear deformation pattern of NTs in austenitic stainless steel by combining in situ tensile tests with a dislocation-based theoretical model and molecular dynamics simulations. Deformation NTs are observed in situ using a transmission electron microscope in different sample regions containing NTs with twin-lamella-spacing (λ) varying from a few nanometers to hundreds of nanometers. Two deformation transitions are found experimentally: from coactivated twinning/detwinning (λ < 5 nm) to secondary twinning (5 nm < λ < 129 nm), and then to the dislocation glide (λ > 129 nm). The simulation results are highly consistent with the observed strong λ-effect, and reveal the intrinsic transition mechanisms induced by partial dislocation slip.

Doping effect and fluorescence quenching mechanism of N-doped graphene quantum dots in the detection of dopamine.

Element doping is recognized as a powerful way to modify surface defect structure and further enhance the fluorescence performance of graphene quantum dots (GQDs). N-doped, S-doped and S, N co-doped GQDs were synthesized to explore the influence of element doping on fluorescence sensing of dopamine (DA) biomolecules. Two interesting works are found, one is that the N-doped GQDs with urea as N source are more effective than the S-doped and S,N co-doped GQDs, characterized by the higher quantum yield (QY) up to 78% and sensitive fluorescence quenching performance to DA. The other is that the N-doped GQDs with ethylenediamine as N source have the highest QY up to 95%, however, exhibits no quenching performance to DA. This abnormal observation is discussed based on the microstructure analysis. Under the optimal reaction condition, the N-doped GQDs exhibit a dual linear relationship of quenching intensity with DA concentration in the range of 10-3000 nM and 3000-7000 nM with detection limits of 3.3 and 611 nM, respectively. The quenching mechanism of N-doped GQDs toward DA is explored from the view of N chemical states, biomolecule structure of DA homologues and redox reaction of DA.

Autoimmune blistering disorders in the setting of human immunodeficiency virus infection.

The interplay between immune dysfunction and human immunodeficiency virus (HIV) is complex. Reports of autoimmune disorders including autoimmune bullous disorders (AIBDs) have been increasing in prevalence in the HIV population since the introduction of highly active antiretroviral therapy in 1995. We offer a literature review of clinical experiences in various AIBDs with particular emphasis on therapeutic management as well as a brief overview of the mechanisms that explain the relationship between AIBD and HIV. Because immunosuppressants are first-line therapies for AIBD treatment, careful consideration is warranted when considering management in the HIV population.

Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy.

OBJECTIVE: To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. METHODS & RESULTS: Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. CONCLUSION: Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.

Hepatitis C virus upregulates B-cell receptor signaling: a novel mechanism for HCV-associated B-cell lymphoproliferative disorders.

B-cell receptor (BCR) signaling is essential for the development of B cells and has a critical role in B-cell neoplasia. Increasing evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B cells of HCV-infected patients and show that HCV upregulates BCR signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and was upregulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, contributing to a better understanding of the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders.

Accuracy of Preoperative Imaging in Detecting Nodal Extracapsular Spread in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: The increasing impact of diagnosing extracapsular spread by using imaging, especially in patients with oropharyngeal squamous cell carcinoma, highlights the need to rigorously evaluate the diagnostic accuracy of imaging. Previous analysis suggested 62.5%-80.9% sensitivity and 60%-72.7% specificity. Our goals were to evaluate the accuracy of imaging in diagnosing extracapsular spread in a cohort of patients with oral cavity squamous cell carcinoma (pathologic confirmation of extracapsular spread routinely available), as a proxy for oropharyngeal squamous cell carcinoma, and to independently assess the reliability of imaging features (radiographic lymph node necrosis, irregular borders/stranding, gross invasion, and/or node size) in predicting pathologically proven extracapsular spread. MATERIALS AND METHODS: One hundred eleven consecutive patients with untreated oral cavity squamous cell carcinoma and available preoperative imaging and subsequent lymph node dissection were studied. Two neuroradiologists blinded to pathologically proven extracapsular spread status and previous radiology reports independently reviewed all images to evaluate the largest suspicious lymph node along the expected drainage pathway. Radiologic results were correlated with pathologic results from the neck dissections. RESULTS: Of 111 patients, 29 had radiographically determined extracapsular spread. Pathologic examination revealed that 28 of 111 (25%) had pathologically proven extracapsular spread. Imaging sensitivity and specificity for extracapsular spread were 68% and 88%, respectively. Radiographs were positive for lymph node necrosis in 84% of the patients in the pathology-proven extracapsular spread group and negative in only 7% of those in the pathologically proven extracapsular spread-negative group. On logistic regression analysis, necrosis (P = .001), irregular borders (P = .055), and gross invasion (P = .068) were independently correlated with pathologically proven extracapsular spread. CONCLUSIONS: Although the specificity of cross-sectional imaging for extracapsular spread was high, the sensitivity was low. Combined logistic regression analysis found that the presence of necrosis was the best radiologic predictor of pathologically proven extracapsular spread, and irregular borders and gross invasion were nearly independently significant.

Walking deficits and centrophobism in an α-synuclein fly model of Parkinson's disease.

Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human α-synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of walking deficits, as seen in aged A30P flies. Psychiatric problems are common in PD patients with anxiety affecting 40-69% of patients. Central avoidance is one assessment of anxiety in various animal models. We found old but not young A30P flies exhibited increased centrophobism, suggesting possible elevated anxiety. Here, we report the first quantitative measures of walking qualities in a PD fly model and propose an alternative behavior paradigm for evaluating motor functions apart from climbing assay.

Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip.

AIMS/HYPOTHESIS: The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B(Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt(caAkt (Tg)) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A (p21(Cip)). In the present study, we sought to assess the mechanisms responsible for augmented p21(Cip) levels in caAkt(Tg) mice and test the role of p21(Cip) in the proliferative responses induced by activation of Akt signalling. METHODS: To gain a greater understanding of the relationship between Akt and p21(Cip), we evaluated the mechanisms involved in the modulation of p2(Cip) by Akt and the in vivo role of reduced p21(Cip) in proliferative responses induced by Akt. RESULTS: Our experiments showed that Akt signalling regulates p21(Cip) transcription and protein stability. caAkt(Tg) /p21(Cip+/-) mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAkt(Tg) mice. Glucose tolerance tests revealed improved glucose tolerance in caAkt(Tg)/p21(Cip+/-) mice compared with caAkt (Tg). These changes resulted from increased proliferation, survival and beta cell mass in caAkt(Tg)/p21(Cip+/-) compared with caAkt(Tg) mice. CONCLUSIONS/INTERPRETATION: Our data indicate that increased p21(Cip) levels in caAkt(Tg) mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that p21(Cip) could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance.

THE AUTODIGESTION HYPOTHESIS AND RECEPTOR CLEAVAGE IN DIABETES AND HYPERTENSION.

One of the key features of cardiovascular complications, such as hypertension or diabetes, is that they often appear at the same time in the same individual together with other forms of co-morbidities. While clinically a recognized phenomenon, no molecular mechanism for such co-morbidities has received universal acceptance. We propose a new hypothesis that provides a molecular basis for co-morbidities in hypertension due to unchecked proteolytic activity and receptor destruction. Testing of the hypothesis in the spontaneously hypertensive rat reveals an unchecked matrix metalloproteinase and serine protease activity in plasma and on several cardiovascular and parenchymal cells. The elevated proteolytic activity causes extracellular cleavage of multiple receptor types, such that cleavage of one receptor type leads to loss of the function carried out by this receptor. Proteolytic cleavage of the extracellular domain of the ß(2) adrenergic receptor in arteries and arterioles causes vasoconstriction and elevation of the central blood pressure while cleavage of the extracellular domain of the insulin receptor leads to insulin resistance and lack of transmembrane glucose transport. A diverse set of cell dysfunctions in the spontaneously hypertensive rat are accompanied by cleavage of the membrane receptors that are involved in these functions. Chronic inhibition of the unchecked protease activity in the spontaneously hypertensive rat serves to restore the extracellular receptor density and alleviates the corresponding cell dysfunctions. The mild unchecked proteolytic activity in the spontaneously hypertensive rat points towards a chronic autodigestion process as a contributor to the end organ injury encountered in this rat strain. The presence of various soluble receptors, which consist of extracellular fragments of membrane receptors, in the plasma of hypertensive and diabetic patients suggest that the autodigestion process may also be present in man.

Depletion and recovery of lymphoid subsets following morphine administration.

BACKGROUND AND PURPOSE: Opioid use and abuse has been linked to significant immunosuppression, which has been attributed, in part, to drug-induced depletion of lymphocytes. We sought to define the mechanisms by which lymphocyte populations are depleted and recover following morphine treatment in mice. EXPERIMENTAL APPROACH: Mice were implanted with morphine pellets and B- and T-cell subsets in the bone marrow, thymus, spleen and lymph nodes were analysed at various time points. We also examined the effects of morphine on T-cell development using an ex vivo assay. KEY RESULTS: The lymphocyte populations most susceptible to morphine-induced depletion were the precursor cells undergoing selection. As the lymphocytes recovered, more lymphocyte precursors proliferated than in control mice. In addition, peripheral T-cells displayed evidence that they had undergone homeostatic proliferation during the recovery phase of the experiments. CONCLUSIONS AND IMPLICATIONS: The recovery of lymphocytes following morphine-induced depletion occurred in the presence of morphine and via increased proliferation of lymphoid precursors and homeostatic proliferation of T-cells.

Staged hernia repair preceded by gastric bypass for the treatment of morbidly obese patients with complex ventral hernias.

BACKGROUND: Obesity may be the most predominant risk factor for recurrence following ventral hernia repair. This is secondary to significantly increased intra-abdominal pressures, higher rates of wound complications, and the technical difficulties encountered due to obesity. Medically managed weight loss prior to surgery is difficult. One potential strategy is to provide a surgical means to correct patient weight prior to hernia repair. METHODS: After institutional review board approval, we reviewed the medical records of all patients who underwent gastric bypass surgery prior to the definitive repair of a complex ventral hernia at our medical center. RESULTS: Twenty-seven morbidly obese patients with an average of 3.7 (range 1-10) failed ventral hernia repairs underwent gastric bypass prior to definitive ventral hernia repair. Twenty-two of the gastric bypasses were open operations and five were laparoscopic. The patients' average pre-bypass body mass index (BMI) was 51 kg/m2 (range 39-69 kg/m2), which decreased to an average of 33 kg/m2 (range 25-37 kg/m2) at the time of hernia repair at a mean of 1.3 years (range 0.9-3.1 years) after gastric bypass. Seven patients had hernia repair at the same time as their gastric bypass (four sutured, three biologic mesh), all of which recurred. Of the 27 patients, 19 had an open hernia repair and eight had a laparoscopic repair. Panniculectomy was performed concurrently in 15 patients who had an open repair. Prior to formal hernia repair, one patient required an urgent operation to repair a hernia incarceration and a small-bowel obstruction 11 months after gastric bypass. The average hernia and mesh size was 203 cm2 (range 24-1,350 cm2) and 1,040 cm2 (range 400-2,700 cm2), respectively. There have been no recurrences at an average follow-up of 20 months (range 2 months-5 years). CONCLUSION: Gastric bypass prior to staged ventral hernia repair in morbidly obese patients with complex ventral hernias is a safe and definitive method to effect weight loss and facilitate a durable hernia repair with a possible reduced risk of recurrence.

Radiation shielding evaluation of the BNCT treatment room at THOR: a TORT-coupled MCNP Monte Carlo simulation study.

This study investigates the radiation shielding design of the treatment room for boron neutron capture therapy at Tsing Hua Open-pool Reactor using "TORT-coupled MCNP" method. With this method, the computational efficiency is improved significantly by two to three orders of magnitude compared to the analog Monte Carlo MCNP calculation. This makes the calculation feasible using a single CPU in less than 1 day. Further optimization of the photon weight windows leads to additional 50-75% improvement in the overall computational efficiency.

Dalbavancin: a novel antimicrobial.

The increasing incidence of serious infections because of Gram-positive pathogens and the rising cost in parenteral administration of antimicrobials has inspired the development of a novel antibiotic. Dalbavancin is the first once a week antibiotic with activity against a broad range of Gram-positive pathogens. A large multicentre, pivotal, Phase III clinical trial, which included 854 patients with complicated skin and skin structure infections, compared 1-2 doses of dalbavancin vs. linezolid. The results demonstrated non-inferiority and a comparable safety profile. With its unique pharmacokinetic profile, ease of use and excellent safety profile, dalbavancin should provide a valuable addition to the armamentarium used to treat infections because of Gram-positive cocci.

Widely tunable optical parametric generation in a photonic crystal fiber.

We report on the observation of widely tunable optical parametric generation in a photonic crystal fiber. The frequency shift of the generated sidebands that arise from modulational instability is strongly dependent on the detuning of the pump from the fiber's zero-dispersion wavelength. We are able to demonstrate experimentally more than 450 nm of sideband tunability as we tune the pump wavelength over 10 nm. Excellent agreement has been found between the experimentally measured and theoretically predicted shifts.

Characterization of chromatic dispersion in photonic crystal fibers using scalar modulation instability.

A simple and accurate method is proposed for characterizing the chromatic dispersion of high air-filling fraction photonic crystal fibers. The method is based upon scalar modulation instability generated by a strong pump wave propagating near the zero-dispersion wavelength. Measuring the modulation instability sideband frequency shifts as a function of wavelength gives a direct measurement of the fiber's chromatic dispersion over a wide wavelength range. To simplify the dispersion calculation we introduce a simple analytical model of the fiber's dispersion, and verify its accuracy via a full numerical simulation. Measurements of the chromatic dispersion of two different types of high air-filling fraction photonic crystal fibers are presented.

Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity.

BACKGROUND: The purpose of this study was to determine whether coronary artery bypass grafting without cardiopulmonary bypass (off-pump CABG) decreases risk-adjusted operative death and major complications after coronary artery bypass grafting in selected patients. METHODS: Using The Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database, procedural outcomes were compared for conventional and off-pump CABG procedures from January 1, 1998, through December 31, 1999. Mortality and major complications were examined, both as unadjusted rates and after adjusting for known base line patient risk factors. RESULTS: A total of 126 experienced centers performed 118,140 total CABG procedures. The number of off-pump CABG cases was 11,717 cases (9.9% of total cases). The use of an off-pump procedure was associated with a decrease in risk-adjusted operative mortality from 2.9% with conventional CABG to 2.3% in the off-pump group (p < 0.001). The use of an off-pump procedure decreased the risk-adjusted major complication rate from 14.15% with conventional CABG to 10.62% in the off-pump group (p < 0.0001). Patients receiving off-pump procedures were less likely to die (adjusted odds ratio 0.81, 95% CI 0.70 to 0.91) and less likely to have major complications (adjusted odds ratio 0.77, 95% CI 0.72 to 0.82). CONCLUSIONS: Off-pump CABG is associated with decreased mortality and morbidity after coronary artery bypass grafting. Off-pump CABG may prove superior to conventional CABG in appropriately selected patients.

Pelvic embolization for treatment of hemorrhage related to spontaneous and induced abortion.

OBJECTIVE: Presentation of outcomes of pelvic arterial embolization for hemorrhage after spontaneous or induced abortion. STUDY DESIGN: We collected case reports of embolization after spontaneous or induced abortion from oral presentations and from members of the National Abortion Federation. RESULTS: Pelvic arterial embolization was performed for 11 women who had hemorrhage after spontaneous or induced abortion, and it was initially successful for all women. One woman ultimately required a hysterectomy after unsuccessful repeated embolization. Prophylactic embolization was done for 8 women who were at risk for hemorrhage from placenta accreta; 4 of these women had subsequent hysterectomies. CONCLUSIONS: Selective pelvic arterial embolization may be a successful treatment for hemorrhage associated with spontaneous and induced abortion. Embolization can be considered before hysterectomy is undertaken for control of hemorrhage. There may be a role for prophylactic catheterization or embolization when there is a risk of severe hemorrhage.