N-terminal pro-B-type natriuretic peptide and D-dimer combined with left atrial diameter to predict the risk of ischemic stroke in nonvalvular atrial fibrillation.

OBJECTIVES: We aimed to explore the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP), d-dimer, and the echocardiographic parameter left atrial diameter (LAD) in identifying and predicting the occurrence of ischemic stroke (IS) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We conducted a retrospective study of 445 patients with NVAF in the First Affiliated Hospital of Nanchang University. They were divided into the NVAF (309 cases) and NVAF with stroke (136 cases) groups according to whether acute ischemic stroke (AIS) occurred at admission. Multivariate logistic regression was used to analyze the odds ratio (OR) of NT-proBNP, d-dimer, and LAD for IS. The predictive value of NT-proBNP, d-dimer, and LAD in identifying the occurrence of IS in NVAF was determined by plotting the receiver operating characteristic (ROC) curves. RESULTS: NT-proBNP, d-dimer, and LAD levels were significantly higher in the NVAF with stroke group than in the NVAF group (p < .05). NT-ProBNP, d-dimer, and LAD were independently associated with IS in NVAF patients (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.08-1.16; OR = 1.87, 95% CI: 1.37-2.55; OR = 1.21, 95% CI: 1.13-1.28, p < .01). The optimal cutoff points for NT-ProBNP, d-dimer, and LAD levels to distinguish the NVAF group from the NVAF with stroke group were 715.0 pg/ml, 0.515 ng/ml, and 38.5 mm, respectively, with the area under the curve (AUC) being [0.801 (95% CI: 0.76-0.84); 0.770 (95% CI: 0.72-0.85); 0.752 (95% CI: 0.71-0.80), p < .01]. The combined score of NT-proBNP, d-dimer, and LAD improved the predictive efficacy of the single index, with an AUC of 0.846 (95% CI: 0.81-0.88, p < .01), sensitivity of 77.2%, and specificity of 76.4%. CONCLUSION: NT-proBNP, d-dimer, and the echocardiographic parameter LAD have outstanding value in predicting the risk of IS in patients with NVAF.

Indoles Oxidative Ring-Opening/Cyclization Cascade with the 1,2-Diaminoarenes: Direct Synthesis of 2-Aryl-3-(2-aminoaryl)quinoxalines.

A mild oxidative sequential tandem reaction was developed to rapidly generate 2-aryl-3-(2-aminoaryl) quinoxalines. This method exploited 2-substituted indoles as substrate to form quinoxalines in a one-pot reaction. The key to this tandem reaction was the formation of 3-iodoindoles, which underwent Kornblum-type oxidation with DMSO to generate active imine 2-substitued 3H-indol-3-ones. The active imines were captured in situ by 1,2-diaminobenzenes to construct diverse quinoxalines. The transformation can be accomplished at room temperature with excellent functional group tolerance.

Synthesis and evaluation of antitumor activity of dibenzodiazepine derivatives.

A series of dibenzodiazepine 2-position derivatives, bearing N-methylpiperazine at the C-11 position, were prepared by using a concise approach. Their inhibitory activities of tumor cell proliferation in vitro were tested in five cell lines, including breast cancer cell BCAP37, gastric cancer cell SGC7901, liver cancer cell HepG2, cervical cancer cell HeLa and acute promyelocytic leukemia cell HL-60. Several compounds showed efficient tumor activity with IC50 values down to 0.30 µM. These compounds are expected to be a new class of potential anticancer lead compounds.

De Winter syndrome as an emergency electrocardiogram sign of ST-elevation myocardial infarction: a case report.

The case report aims to reveal de Winter's electrocardiogram (ECG) pattern as an equivalent to anterior ST-segment elevation myocardial infarction (STEMI). We report a case of a 49-year-old man with a history of smoking who presented to the emergency department with a 1 day history of chest pain that was exacerbated 5 h prior to presentation. Detailed clinical investigations and coronary angiographic characteristics were recorded. The first ECG of the patient was consistent with de Winter syndrome. Acute coronary artery angiography showed that the proximal left anterior descending coronary artery was completely occluded after the first diagonal branch artery was given off. A percutaneous coronary intervention was immediately performed. Our case indicates that early identification and diagnosis of such ECGs and timely reperfusion therapy of de Winter syndrome as a STEMI equivalent are required to improve the prognosis of such patients.

High-performance solar-blind SnO2 nanowire photodetectors assembled using optical tweezers.

One-dimensional semiconducting SnO2 nanowires with wide bandgaps are promising candidates to build many important optoelectronic devices. Because building these devices involves the assembly of nanowires into complex structures, manipulation of the active materials needs to be done with high spatial precision. In this paper, an optical tweezer system, comprising a spatial light-modulator, a microscope, and optical elements, is used to individually trap, transfer, and assemble SnO2 nanowires into two-terminal photodetectors in a liquid environment. After the assembly using optical trapping, the two ends of the SnO2 nanowire photodetectors, which are connected with the electrodes, were further stabilized using a focused laser. During exposure to 275 nm deep-ultraviolet light, the as-assembled photodetectors show a high Iph/Idark ratio of 2.99 × 105, a large responsivity of 4.3 × 104 A W-1, an excellent external quantum efficiency of 1.94 × 105, and a high detectivity of 2.32 × 1013 Jones. The photoresponse-speed of the devices could be improved further using passivation with a polymer. The rise and decay times are about 60 ms and 100 ms, respectively. As a result of this study, we can confirm that non-contact optical trapping can enable the construction of nanowire architectures for optoelectronic, bioelectronic, and other devices.

[Comparative study of processed autogenous tooth bone and xenogeneic bovine bone in repairing an alveolar bone defect].

OBJECTIVE: This study was conducted to counter the osteogenesis effects of processed autogenous tooth bone and xenogeneic bovine bone following tooth extraction and to provide an experimental basis for clinical applications. METHODS: Central incisors were extracted with general anesthesia on both sides of a maxillary arch in 12 rabbits, which were randomly divided into three groups, thereby containing four rabbits in each group. Three rabbits were assigned to the experimental groups and one was for the control group. In the experimental groups, the xenogeneic bovine bone was applied to the left incisor socket, whereas the processed autogenous tooth bone was applied to the right incisor socket. The blank control group only extracted the teeth and did not implant any bone powder. The three groups died after 4, 8, and 12 weeks, respectively. A mineralization degree of new bone tissues was observed by fluorescence staining and the formation of a new bone was observed by histology. RESULTS: The sedimentary mineralization rate was greater in the processed autogenous tooth bone than in the xenogeneic bovine bone (P<0.05). The trabecular bone of the xenogeneic bovine bone was sparse and slender. The left sockets, which were filled with the xenogeneic bovine bone, had more woven and less lamellar bones than the right sockets, which were filled with the processed autogenous tooth bone. CONCLUSIONS: The processed autogenous tooth bone offers more advantages as a bone-grafting material than the xenogeneic bovine bone in terms of bone increment.

Discovery of a low-systemic-exposure DGAT-1 inhibitor with a picolinoylpyrrolidine-2-carboxylic acid moiety.

A series of diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors with a picolinoylpyrrolidine-2-carboxylic acid moiety were designed and synthesized. Of these compounds, compound 22 exhibited excellent DGAT-1-inhibitory activity (hDGAT-1 enzyme assay, 50% inhibitory concentration [IC50]=3.5±0.9nM) and effectively reduced the intracellular triglyceride contents in 3T3-L1, HepG2 and Caco-2 cells. A preliminary study of the plasma and tissue distributions of compound 22 in mice revealed low plasma exposure and high concentrations in different segments of the intestine and liver, which may facilitate targeting DGAT-1. Furthermore, in an acute lipid challenge test, compound 22 showed a dose-dependent inhibitory effect on high-serum triglycerides in C57/KSJ mice induced by olive oil (1, 3, and 10mg/kg, i.g.).

Postictal generalized EEG suppression after generalized convulsive seizures: A double-edged sword.

OBJECTIVE: The aim of this study is to investigate the key facilitating factors for postictal generalized EEG suppression (PGES) in a large cohort of patients with generalized convulsive seizures (GCSs). METHODS: We retrospectively reviewed the data of consecutive patients who had GCSs in the epilepsy monitoring units of two epilepsy centers. Statistical analysis was performed to assess specific variables as potential risk factors for PGES. RESULTS: Among the 208 enrolled patients with 366 seizures, PGES was observed in 109 (51.9%) patients and 168 (45.9%) GCSs. The mean duration of PGES was 33.2 ± 12.0 s (34 s, 3-70 s). PGES or severe PGES (>20 s) was associated with more severe postictal coma and temporal lobe epilepsy. Moreover, PGES was independently associated with a longer tonic duration, shorter total seizure duration, and lower habitual seizure frequency. CONCLUSIONS: PGES is strongly correlated not only with longer tonic duration, but also with shorter total seizure duration and lower habitual seizure frequency. SIGNIFICANCE: PGES may represent a switch-off inhibitory mechanism in seizure termination; moreover, it may indicate the efficacy of a long-lasting inhibitory network that suppresses GCS ictogenesis.

Synthesis and antitumor activity evaluation of lamiridosin A derivatives.

A series of lamiridosin A derivatives were synthesized through simple procedures. Their antitumor activities were evaluated against EC9706, MGC803, and B16 cell lines in vitro. Several compounds showed potent antitumor activity, especially compound 10, with IC50 value of 2.36 µmol/L against MGC803 cell lines, is more potent than marketed positive drug 5-fluorouridine (5-FU).

Highly efficient synthesis of quinoxaline derivatives from 1,2-benzenediamine and α-aminoxylated 1,3-dicarbonyl compounds.

Simple and efficient synthetic procedures for the preparation of quinoxaline, pyrazine, pyridopyrazine, and benzoxazin-2-one derivatives were developed. The one-pot cascade process involves the acidic elimination of α-aminoxylated dicarbonyl compounds to generate 1,2,3-tricarbonyl compounds and subsequent condensation with 1,4-N,N or -N,O dinucleophiles to afford quinoxaline, pyrazine, pyridopyrazine, and benzoxazin-2-one scaffolds. All the proposed processes do not need extra catalysts, dry solvents, or harsh reaction conditions.

Analyzing reliability of seizure diagnosis based on semiology.

This study aimed to determine the accuracy of seizure diagnosis by semiological analysis and to assess the factors that affect diagnostic reliability. A total of 150 video clips of seizures from 50 patients (each with three seizures of the same type) were observed by eight epileptologists, 12 neurologists, and 20 physicians (internists). The videos included 37 series of epileptic seizures, eight series of physiologic nonepileptic events (PNEEs), and five series of psychogenic nonepileptic seizures (PNESs). After observing each video, the doctors chose the diagnosis of epileptic seizures or nonepileptic events for the patient; if the latter was chosen, they further chose the diagnosis of PNESs or PNEEs. The overall diagnostic accuracy rate for epileptic seizures and nonepileptic events increased from 0.614 to 0.660 after observations of all three seizures (p < 0.001). The diagnostic sensitivity and specificity of epileptic seizures were 0.770 and 0.808, respectively, for the epileptologists. These values were significantly higher than those for the neurologists (0.660 and 0.699) and physicians (0.588 and 0.658). A wide range of diagnostic accuracy was found across the various seizures types. An accuracy rate of 0.895 for generalized tonic-clonic seizures was the highest, followed by 0.800 for dialeptic seizures and then 0.760 for automotor seizures. The accuracy rates for myoclonic seizures (0.530), hypermotor seizures (0.481), gelastic/dacrystic seizures (0.438), and PNESs (0.430) were poor. The reliability of semiological diagnosis of seizures is greatly affected by the seizure type as well as the doctor's experience. Although the overall reliability is limited, it can be improved by observing more seizures.

Gold-catalyzed reactions of 3-alkynyloxireno[2, 3-b]chromenones to form 3(2H)-furanones via a domino pathway.

3(2H)-Furanones are efficiently generated from 3-alkynyl oxireno[2,3-b]chromenones by an Au/DDQ-catalyzed domino reaction through a pathway composed of cyclization, C-C cleavage, nucleophilic addition, oxidation, and nucleophilic addition. It was found that stoichiometric AuCl(3) or catalytic Au with stoichiometric DDQ can oxidize the benzylic sp(3) C-H bond to facilitate nucleophilic addition.

Direct synthesis of functional azaxanthones by using a domino three-component reaction.

NH aldimines, generated in situ from the corresponding aldehydes by reaction with ammonium acetate, serve as nitrogen nucleophiles in reactions with 3-(1-alkynyl)chromones and 3-cyanochromones that generate functionalized azaxanthones. These processes take place under mild conditions that do not require dry solvents. The products of the reactions described represent new chemical entities. We believe that the newly developed cascade process will serve as a potent method for the synthesis of N-heterocycles and in diversity-oriented synthesis.

Synthesis and biological evaluation of novel amprenavir-based P1-substituted bi-aryl derivatives as ultra-potent HIV-1 protease inhibitors.

A series of P1-substituted biaryl amprenavir derivatives was designed and synthesized. These compounds were evaluated for enzyme inhibition and antiviral activity in vitro. Several compounds showed highly efficient antiviral activity with EC(50) values down to 0.10nM, which are more potent than marketed HIV-1 protease inhibitors. Docking study indicated that 12c has similar binding mode to amprenavir with full occupancy in P1.

Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice.

AIM: To test whether pharmacological inhibition of Diacylglycerol acyltransferase 1 (DGAT1) by a small-molecule inhibitor H128 can improve metabolism disorders in leptin receptor-deficient db/db mice. METHODS: To investigate the effect of H128 on intestinal fat absorption,db/db mice were acutely given a bolus of corn oil by gavage. The mice were further orally administered H128 (3 and 10 mg/kg) for 5 weeks. Blood glucose, lipids, insulin, ALT, and AST as well as hepatic triglycerides were measured. The insulin tolerance test was performed to evaluate insulin sensitivity. The expression of genes involved in fatty acid oxidation was detected by RT-PCR. RESULTS: Oral administration of H128 (10 mg/kg) acutely inhibited intestinal fat absorption following a lipid challenge in db/db mice. Chronic treatment with H128 significantly inhibited body weight gain, decreased food intake, and induced a pronounced reduction of serum triglycerides. In addition, H128 treatment markedly ameliorated hepatic steatosis, characterized by decreased liver weight, lipid droplets, and triglyceride content as well as serum ALT and AST levels. Furthermore, H128 treatment increased the expression of the CPT1 and PPARα genes in liver, suggesting that H128 enhanced fatty acid oxidation in db/db mice. However, neither blood glucose nor insulin tolerance was affected by H128 treatment throughout the 5-week experimental period. CONCLUSION: DGAT1 may be an effective therapeutic target for the treatment of obesity, hyperlipidemia and hepatic steatosis.