Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth.

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

Microtiter plate-based chemistry and in situ screening: SuFEx-enabled lead discovery of selective AChE inhibitors.

Sulphur fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulphur connective hubs. Here, we reported an efficient synthesis and in situ screening method for building a library of sulphonamides on the picomolar scale by SuFEx reaction between a sulphonyl fluoride (RSO2F) core and primary or secondary amines. This biocompatible SuFEx reaction would allow us to rapidly synthesise sulphonamide molecules, and evaluate their ChE inhibitory activity. Compound T14-A24 was identified as a reversible, competitive, and selective AChE inhibitor (Ki = 22 nM). The drug-like evaluation showed that T14-A24 had benign BBB penetration, remarkable neuroprotective effect, and safe toxicological profile. In vivo behavioural study showed that T14-A24 treatment improved the Aß1 - 42-induced cognitive impairment, significantly prevented the effects of Aß1 - 42 toxicity. Therefore, this SuFEx click reaction can accelerate the discovery of lead compounds.

Physiology-Based Pharmacokinetic Study on 18ß-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats.

To understand that 18ß-Glycyrrhetic acid 3-O-mono-ß-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18ß-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18ß-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.

Fluorosulfate-containing pyrazole heterocycles as selective BuChE inhibitors: structure-activity relationship and biological evaluation for the treatment of Alzheimer's disease.

Novel scaffolds are expected to treat Alzheimer's disease, pyrazole-5-fluorosulfates were found as selective BuChE inhibitors. Compounds K1-K26 were assayed for ChE inhibitory activity, amongst them, compound K3 showed potent BuChE and hBuChE inhibition (IC50 = 0.79 µM and 6.59 µM). SAR analysis showed that 1-, 3-, 4-subtituent and 5-fluorosulfate of pyrazole ring affected BuChE inhibitory activity. Molecular docking showed that the fluorosulfate increased the binding affinity of hBuChE through π-sulphur interaction. Compound K3 was a reversible, mixed and non-competitive BuChE inhibitor (Ki = 0.77 µM) and showed remarkable neuroprotection, safe toxicological profile and BBB penetration. In vivo behavioural study showed that K3 treatment improved the Aß1 - 42-induced cognitive impairment, and significantly prevented the effects of Aß1 - 42 toxicity. Therefore, selective BuChE inhibitor K3 has potential to be further developed as AD therapeutics.

Genetic Characteristics of Resectable Colorectal Cancer with Pulmonary Metastasis.

The lung is the most common extra-abdominal metastasis site of colorectal cancer (CRC). This study aimed to investigate the genetic variation of pulmonary metastases (PM) and primary tumors in resectable CRC. The clinical data of 410 patients with PM after CRC surgery and 33 paraffin-embedded tissue samples from January 2012 to July 2019 in our hospital were collected retrospectively. Next, 450-panel gene detection technologies based on next-generation sequencing (NGS) were used to analyze the changes in the gene map and the overall variation in cancer-related genes in PM and primary tumors. After quality control, 19 samples were included in the final gene analysis. The results showed that APC (89.5%), TP53 (89.5%), and KRAS (53%) were the most common mutations in PM and primary tumors, but the gene amplification variation was enriched in primary tumors (4.6% vs. 11.4%). KRAS G12D was the most common site variation of the KRAS gene in both PM and primary tumors of CRC. There was no hotspot mutation in the TP53 locus in CRC, and the TP53 mutation in the PM was consistent with that in the primary lesion. The microsatellite instability (MSI) levels of 10 patients were MSS. The mean tumor mutation burden (TMB) of the primary tumor (5.3 muts·Mb-1) was slightly higher than that of metastasis (5.0 muts·Mb-1). In our institution, the genetic characteristics of resectable PM from CRC may be highly consistent with those of the primary tumor.

Brainstem auditory evoked potential combined with high resolution cranial base CT can optimize the diagnosis of auditory nerve injury.

PURPOSE: Auditory nerve injury is one of the most common nerve injury complications of skull base fractures. However, there is currently a lack of auxiliary examination methods for its direct diagnosis. The purpose of this study was to find a more efficient and accurate means of diagnosis for auditory nerve injury. METHODS: Through retrospectively analyzing the results of brainstem auditory evoked potential (BAEP) and high-resolution CT (HRCT) in 37 patients with hearing impairment following trauma from January 1, 2018 to July 31, 2020, the role of the two inspection methods in the diagnosis of auditory nerve injury was studied. Inclusion criteria were patient had a clear history of trauma and unilateral hearing impairment after trauma; while exclusion criteria were: (1) severe patient with a Glasgow coma scale score ≤5 because these patients were classified as severe head injury and admitted to the intensive care unit, (2) patient in the subacute stage admitted 72 h after trauma, and (3) patient with prior hearing impairment before trauma. According to Goodman's classification of hearing impairment, the patients were divided into low/medium/severe injury groups. In addition, patients were divided into HRCT-positive and negative groups for further investigation with their BAEP results. The positive rates of BEAP for each group were observed, and the results were analyzed by Chi-square test (p < 0.05, regarded as statistical difference). RESULTS: A total of 37 patients were included, including 21 males and 16 females. All of them were hospitalized patients with GCS score of 6-15 at the time of admission. The BAEP positive rate in the medium and severe injury group was 100%, which was significantly higher than that in the low injury group (27.27%) (p < 0.01). The rate of BEAP positivity was significantly higher in the HRCT-positive group (20/30, 66.7%) than in the HRCT-negative group (1/7, 14.3%) (p < 0.05). Twenty patients (54.05%) were both positive for BEAP and HRCT test, and considered to have auditory nerve damage. Six patients (16.22%) were both negative for BEAP and HRCT test, and 10 patients (27.03%) were BAEP-negative but HRCT-positive: all the 16 patients were considered as non-neurological injury. The rest 1 case (2.70%) was BAEP-positive but HRCT-negative, which we speculate may have auditory nerve concussion. CONCLUSION: By way of BAEP combining with skull base HRCT, we may improve the accuracy of the diagnosis of auditory nerve injury. Such a diagnostic strategy may be beneficial to guiding treatment plans and evaluating prognosis.

Atomic Layer Deposition of Ga2O3/ZnO Composite Films for High-Performance Forming-Free Resistive Switching Memory.

The resistive switching behavior in resistive random access memories (RRAMs) using atomic-layer-deposited Ga2O3/ZnO composite film as the dielectric was investigated. By alternatively atomic-layer-depositing Ga2O3 and ZnO with different thickness, we can accurately control the oxygen vacancy concentration. When regulating ZnO to ∼31%, the RRAMs exhibit a forming-free property as well as outstanding performance, including the ratio of a high resistance state to the low resistance state of 1000, retention time of more than 1 × 104 s, and the endurance of 100. By preparing RRAMs of different Zn concentration, we carried out a comparative study and explored the physical origin for the forming-free property as well as good performance. Finally, a unified model is proposed to account for the resistive switching and the current conduction mechanism, providing meaningful insights in the development of high-quality and forming-free RRAMs for future memory and neuromorphic applications.

Improved Ferroelectric Performance of Mg-Doped LiNbO3 Films by an Ideal Atomic Layer Deposited Al2O3 Tunnel Switch Layer.

Bilayer structures composed of 5% Mg-doped LiNbO3 single-crystal films and ultrathin Al2O3 layers with thickness ranging from 2 to 6 nm have been fabricated by using ion slicing technique combined with atomic layer deposition method. The transient domain switching current measurement results reveal that the P-V hysteresis loops are symmetry in type II mode with single voltage pulse per cycle, which may be attributed to the built-in electric field formed by asymmetric electrodes and compensation of an internal imprint field. Besides, the inlaid Al2O3, as an ideal tunnel switch layer, turns on during ferroelectric switching, but closes during the post-switching or non-switching under the applied pulse voltage. The Al2O3 layer blocks the adverse effects such as by-electrode charge injection and improves the fatigue endurance properties of Mg-doped LiNbO3 ferroelectric capacitors. This study provides a possible way to improve the reliability properties of ferroelectric devices in the non-volatile memory application.

Systematic Study of the SiOx Film with Different Stoichiometry by Plasma-Enhanced Atomic Layer Deposition and Its Application in SiOx/SiO2 Super-Lattice.

Atomic scale control of the thickness of thin film makes atomic layer deposition highly advantageous in the preparation of high quality super-lattices. However, precisely controlling the film chemical stoichiometry is very challenging. In this study, we deposited SiOx film with different stoichiometry by plasma enhanced atomic layer deposition. After reviewing various deposition parameters like temperature, precursor pulse time, and gas flow, the silicon dioxides of stoichiometric (SiO2) and non-stoichiometric (SiO1.8 and SiO1.6) were successfully fabricated. X-ray photo-electron spectroscopy was first employed to analyze the element content and chemical bonding energy of these films. Then the morphology, structure, composition, and optical characteristics of SiOx film were systematically studied through atomic force microscope, transmission electron microscopy, X-ray reflection, and spectroscopic ellipsometry. The experimental results indicate that both the mass density and refractive index of SiO1.8 and SiO1.6 are less than SiO2 film. The energy band-gap is approved by spectroscopic ellipsometry data and X-ray photo-electron spectroscopy O 1s analysis. The results demonstrate that the energy band-gap decreases as the oxygen concentration decreases in SiOx film. After we obtained the Si-rich silicon oxide film deposition, the SiO1.6/SiO2 super-lattices was fabricated and its photoluminescence (PL) property was characterized by PL spectra. The weak PL intensity gives us greater awareness that more research is needed in order to decrease the x of SiOx film to a larger extent through further optimizing plasma-enhanced atomic layer deposition processes, and hence improve the photoluminescence properties of SiOx/SiO2 super-lattices.

The preparation of synthetic graphite materials with hierarchical pores from lignite by one-step impregnation and their characterization as dye absorbents.

Herein, synthetic graphite materials with hierarchical pores and large specific surface area were successfully prepared by one-step impregnation with lignite as the carbon source, sulfuric acid (H2SO4) as the oxidant, and phosphoric acid (H3PO4) as the activator. The microstructural characteristics of synthetic graphite were investigated via X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Moreover, the pore parameters were studied by nitrogen adsorption-desorption. The results showed that synthetic graphite had a perfect orderly layered structure with high graphitization degree and a well-developed multistage pore structure with pore sizes ranging from nanometer to micrometer. The specific surface area and pore volume were 415.29 m2 g-1 and 0.67 cm3 g-1, respectively. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) showed that the impregnation pretreatment provided polar groups containing oxygen to the surfaces. These unique characteristics make synthetic graphite possess good adsorption capacity for dye pollutants (the adsorption rate of the methyl orange solution was 99.9% within 60 min at 50 °C, and the pH value of the solution was 3). The effects of temperature and pH value on the adsorption capacity were studied. The repeatability of the adsorption performance was also tested, and the adsorption rate was 84.6% of the initial adsorption rate after five cycles.

Protective role of microRNA-374 against myocardial ischemia-reperfusion injury in mice following thoracic epidural anesthesia by downregulating dystrobrevin alpha-mediated Notch1 axis.

Ischemia-reperfusion (I/R) injury often leads to myocardial apoptosis and necrosis. Studies have demonstrated the role microRNAs (miRs) played in myocardial I/R injury. Thus, we established a myocardial I/R injury model and a thoracic epidural anesthesia (TEA) model in mice to explore whether microRNA-374 (miR-374) affects myocardial I/R injury. We collected myocardial tissues to evaluate whether TEA exerts a protection effect on myocardial tissues. In addition, the levels of miR-374, dystrobrevin alpha (DTNA), and the statue of the Notch1 axis were detected. Subsequently, cardiomyocytes extracted from TEA mice were treated to regulate their levels of miR-374 and DTNA. After that, cell viability, cell cycle distribution, and apoptosis of cardiomyocytes were assessed. This was followed by the detection of the myocardial infarction area. The mice models of myocardial I/R injury were associated with poorly expressed miR-374 and highly expressed DTNA. TEA was found to protect myocardial tissues against myocardial I/R injury by elevating miR-374 and reducing DTNA. Dual-luciferase reporter assay validated that DTNA was the target gene of miR-374. Cardiomyocytes with overexpressed miR-374 were shown to have downregulated DTNA levels and blocked Notch1 axis. Overexpressed miR-374 was also found to promote the viability and inhibit the apoptosis of cardiomyocytes, as well as to increase the number of cells arrested in the S phase. In accordance with this, the myocardial infarction area was decreased with the upregulated miR-347 and downregulated DTNA. Collectively, these results demonstrated that, by inhibiting the activity of DTNA-mediated Notch1 axis, miR-374 could protect against myocardial I/R injury in mice after TEA.

Engineering yeast with bifunctional minicellulosome and cellodextrin pathway for co-utilization of cellulose-mixed sugars.

BACKGROUND: Consolidated bioprocessing (CBP), integrating cellulase production, cellulose saccharification, and fermentation into one step has been widely considered as the ultimate low-cost configuration for producing second-generation fuel ethanol. However, the requirement of a microbial strain able to hydrolyze cellulosic biomass and convert the resulting sugars into high-titer ethanol limits CBP application. RESULTS: In this work, cellulolytic yeasts were developed by engineering Saccharomyces cerevisiae with a heterologous cellodextrin utilization pathway and bifunctional minicellulosomes. The cell-displayed minicellulosome was two-scaffoldin derived, and contained an endoglucanase and an exoglucanase, while the intracellular cellodextrin pathway consisted of a cellodextrin transporter and a ß-glucosidase, which mimicked the unique cellulose-utilization system in Clostridium thermocellum and allowed S. cerevisiae to degrade and use cellulose without glucose inhibition/repression on cellulases and mixed-sugar uptake. Consequently, only a small inoculation of the non-induced yeast cells was required to efficiently co-convert both cellulose and galactose to ethanol in a single-step co-fermentation process, achieving a high specific productivity of ~62.61 mg cellulosic ethanol/g cell·h from carboxymethyl cellulose and ~56.37 mg cellulosic ethanol/g cell·h from phosphoric acid-swollen cellulose. CONCLUSIONS: Our work provides a versatile engineering strategy for co-conversion of cellulose-mixed sugars to ethanol by S. cerevisiae, and the achievements in this work may further promote cellulosic biofuel production.

Improving the postoperative handover process in the intensive care unit of a tertiary teaching hospital.

AIMS AND OBJECTIVES: The aim of this study was to improve the postoperative handover process and immediate postoperative patient outcomes. The objective was to implement a postoperative handover protocol in the neurosurgical intensive care unit of a tertiary teaching hospital. BACKGROUND: Postoperative handover is a multidisciplinary collaborative medical activity that involves information transfer, sequenced tasks and high-quality teamwork. Evidence suggests that a lack of a standardised postoperative handover protocol adversely influences care quality and potentially compromises patient safety. As there is a lack of such protocols in China, there is an identified need for improvement. DESIGN: This was a pretest/post-test study with follow-up after three months. METHODS: A postoperative handover protocol that included a postoperative handover checklist, a standardised handover pathway and core team member involvement was developed based on research evidence and expert opinions and was then implemented and evaluated. RESULTS: Following the implementation of this protocol, improved teamwork was achieved, surgeons were more frequently present at bedside handovers, the rate of transferring key messages increased, the rate of ventilator weaning within the first six hours of neurosurgical intensive care unit admission increased, and the ventilation duration per patient decreased without any clinical incident occurring in the first 24 hours after neurosurgical intensive care unit admission. CONCLUSIONS: Following the implementation of a tailored standardised handover protocol, communication, teamwork and short-term patient outcomes were improved. RELEVANCE TO CLINICAL PRACTICE: This clinically based research highlights the need for policy makers and administrators to create unit-specific protocols for improving postoperative handovers.

Angiopoietin-1 and Angiopoietin-2 Expression Imbalance Influence in Early Period After Subarachnoid Hemorrhage.

PURPOSE: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional-an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other's expression. METHODS: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6-72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. RESULTS: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. CONCLUSIONS: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

Spectral- and time-domain optical coherence tomography measurements of macular thickness in young myopic eyes.

PURPOSE: To evaluate the variation in macular retinal thickness and volume in young Chinese myopic patients using time-domain optical coherence tomography (Stratus TD-OCT) and spectral-domain optical coherence tomography (Cirrus HD-OCT). METHODS: Ninety-two eyes of 92 myopic subjects were recruited in this study. Based upon spherical equivalence (SE), subjects were divided into two groups: the low to moderate myopia group (-0.5 D ≤ SE < -6.0 D), and the high myopia group (SE ≥ -6.0 D). Stratus TD-OCT and Cirrus HD-OCT were used to compare macular retinal thickness and volume between the two groups. Bland-Altman analysis and Pearson correlation were used to measure agreement between the two OCT systems. RESULTS: Average macular retinal thickness and total macular volume measured by Cirrus HD-OCT and Stratus TD-OCT of the low to moderate myopia group were 283.52 ± 12.14 µm and 245.38 ± 8.55 µm, respectively, and 10.08 ± 0.37 mm3 and 6.85 ± 0.26 mm3, respectively, and the high myopia groups were 269.58 ± 10.72 µm and 235.65 ± 7.54 µm, respectively, and 9.71 ± 0.36 mm3 and 6.52 ± 0.25 mm3, respectively. The measurements of the two OCTs showed that macular retinal thickness of the parafovea was significantly lower in the high myopia group compared with the low to moderate myopia group, except at the fovea (all P-values less than 0.001, except at the fovea). Using the Bland-Altman method and Pearson correlation, measurements of macular thickness in nine macular retinal subfields and total macular volumes showed good agreement between the two OCTs in myopic eyes (all P-values less than 0.001), with better agreement in the low to moderate myopia group than in the high myopia group. CONCLUSIONS: The average macular retinal thickness of the fovea did not vary with myopia, while the total volume and retinal thickness of the parafovea were thinner with increasing myopia. There was good agreement between the two OCTs in myopic eyes in all macular subfields, and the Cirrus HD-OCT system provided thicker macular retinal thickness measurements than the Stratus TD-OCT system. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1683223414107652.

Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54)-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54)-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

The influence of corneal astigmatism on retinal nerve fiber layer thickness and optic nerve head parameter measurements by spectral-domain optical coherence tomography.

BACKGROUND: To evaluate the influence of corneal astigmatism (CA) on retinal nerve fiber layer (RNFL) thickness and optic nerve head(ONH) parameters measured with spectral-domain optical coherence tomography (OCT) in high myopes patients before refractive surgery. METHODS: Seventy eyes of 35 consecutive refractive surgery candidates were included in this study. The mean age of the subjects was 26.42 ± 6.95 years, the average CA was -1.17 diopters (D; SD 0.64; range -0.2 to-3.3D), All subjects in this study were WTR CA. 34 eyes were in the normal CA group with a mean CA was -0.67 ± 0.28D, 36 eyes were in the high CA group with an average CA of -1.65 ± 0.49D. All subjects underwent ophthalmic examination and imaging with the Cirrus HD OCT. RESULTS: No significant difference was noted in the average cup-to-disk ratio, vertical cup-to-disk ratio and cup volume (all P values > 0.05). Compared with the normal CA group, the high CA group had a larger disc area and rim area, thinner RNFL thickness in the temporal quadrant, and the superotemporal and inferotemporal peaks were farther to the temporal horizon (All P values < 0.05). There were no significant differences between the two groups in global average RNFL thickness, as well as superior, nasal and inferior quadrant RNFL thickness (all P values > 0.05). CONCLUSIONS: The degree of with-the-rule CA should be considered when interpreting ONH parameters and peripapillary RNFL thickness measured by the Cirrus HD OCT. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1148475676881895.

Synthesis and antitumor activity of 3-methyl-4-oxo-3,4-dihydroimidazo [5,1-d][1,2,3,5]tetrazine-8-carboxylates and -carboxamides.

Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate and -carboxamide derivatives were synthesized and evaluated for their growth inhibition in seven human solid tumor and a human leukemia HL-60 cell lines. Compound IVa showed more activity than the other compounds and the positive control temozolomide. In the presence of 40 µg/mL of IVa, the survival rate of all tested tumor cells was less than 10%. Esters displayed more potent antitumour activity than amides and temozolomide against HL-60 cells. These compounds also exhibited considerably enhanced water-solubility.

Acute subdural hematoma with swirl signs: clinical analysis of 15 cases.

From July 2003 to July 2009, 15 cases of subdural hematoma with swirl signs were treated in our hospital and their clinical data were retrospectively analysed. The mortality was compared between these patients and those with typical acute subdural hematoma who were treated at the same time in our hospital. Among the 15 cases, full recovery was achieved in 4 cases, slight disability in 2, grave disability in 2 and death in 7 (46.7%). The mortality of these patients was conspicuously higher than that of typical subdural hematoma (14/83, 16.9%, P < 0.01). Subdural hematoma with swirl signs is often suggestive of hazardous pathogenetic condition and early diagnosis and prompt surgical intervention is essential to reduce mortality.

One-pot synthesis of pyrimido[1,6-a]indol-1(2H)-one derivatives by a nucleophilic addition/Cu-catalyzed N-arylation/Pd-catalyzed C-H activation sequential process.

A novel and convenient one-pot synthesis of pyrimido[1,6-a]indol-1(2H)-one derivatives through a nucleophilic addition/Cu-catalyzed N-arylation/Pd-catalyzed C-H activation sequential process is described. The reaction of easily prepared ortho-gem-dibromovinyl isocyanates with N-alkyl-anilines gave the desired indole derivatives in moderate to good yields.