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Glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are two novel classes of hypoglycemic agents. The relative cardiovascular effectiveness between these two drug classes in patients with type 2 diabetes (T2D) is unestablished due to the absence of large cardiovascular outcome trials directly comparing DPP-4i with GLP-1RA. We aimed to incorporate large propensity score-matched cohort studies to conduct a meta-analysis, to determine the relative effectiveness of GLP-1RA versus DPP-4i on cardiovascular endpoints in T2D patients. Compared to DPP-4i, GLP-1RA was associated with the significantly lower risks of major adverse cardiovascular events [MACE] (HR 0.76, 95% CI 0.63-0.92), cardiovascular mortality (HR 0.59, 95% CI 0.37-0.95), myocardial infarction (HR 0.89, 95% CI 0.80-0.98), stroke (HR 0.86, 95% CI 0.76-0.96), and all-cause mortality (HR 0.63, 95% CI 0.42-0.96) in T2D patients; whereas these two drug classes had the similar risk of hospitalization for heart failure [HHF] (HR 0.95, 95% CI 0.77-1.16). Meta-regression analyses showed that six factors (i.e., mean age, female proportion, cardiovascular disease proportion, heart failure proportion, and the proportions of receiving metformin and insulin at baseline) did not significantly affect the effects of GLP-1RA on MACE and HHF (P ≥ 0.076). This meta-analysis provides the direct evidence regarding the relative cardiovascular effectiveness of GLP-1RA versus DPP-4i from real-world studies, and its findings suggest that among T2D patients GLP-1RA should be considered in preference to DPP-4i as for preventing atherosclerotic cardiovascular events and death in clinical practice.

Serum chitinase-3-like protein 1 (CHI3L1) is a potential biomarker for fibrosis assessment. We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virus-related fibrosis.Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B (CHB) patients. Significant fibrosis was defined as a liver stiffness 9.7 kPa. The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic (ROC) analysis.Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis (≥ F2, 81.9 ng/mL) than in those without significant hepatic fibrosis ( F2, 56.5 ng/mL) (P 0.001). In CHB patients, the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6% and 59.1%, respectively, with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728 (95% CI: 0.637-0.820).Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver. Moreover, CHI3L1 is feasible in monitoring disease progression.

Spiroalanpyrroids A (1) and B (2), two sesquiterpene alkaloids with an unprecedented eudesmanolide–pyrrolizidine spiro[5.5] framework, were isolated together with two new sesquiterpene-amino acid adducts, helenalanprolines A (3) and B (4), from the roots of Inula helenium. Their structures were elucidated by spectroscopic data analysis, ECD calculations, and single-crystal X-ray diffraction analysis. A plausible biosynthetic pathway was proposed for 1 and 2. Bioassays showed that compounds 3 and 4 significantly inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 15.8 and 13.5 μM, respectively.

The association between high-dose or low-dose sodium-glucose cotransporter 2 (SGLT2) inhibitors and various cardiovascular and respiratory serious adverse events (SAE) is unclear. Our meta-analysis aimed to define the association between high-dose or low-dose SGLT2 inhibitors and 86 kinds of cardiovascular SAE and 58 kinds of respiratory SAE. We included large cardiorenal outcome trials of SGLT2 inhibitors. Meta-analysis was conducted and stratified by the dose of SGLT2 inhibitors (high dose or low dose) to synthesize risk ratio (RR) and 95% confidence interval (CI). We included 9 trials. Compared with placebo, SGLT2 inhibitors used at high dose or low dose were associated with the decreased risks of 6 kinds of cardiovascular SAE [eg, bradycardia (RR, 0.60; 95% CI, 0.41-0.89), atrial fibrillation (RR, 0.79; 95% CI, 0.69-0.92), and hypertensive emergency (RR, 0.34; 95% CI, 0.15-0.78)] and 6 kinds of respiratory SAE [eg, asthma (RR, 0.59; 95% CI, 0.37-0.93), chronic obstructive pulmonary disease (RR 0.77, 95% CI 0.62-0.96), and sleep apnea syndrome (RR 0.37, 95% CI 0.17-0.81)]. SGLT2 inhibitors used at high dose or low dose did not show significant associations with 132 other cardiopulmonary SAE. For any outcome of interest, the subgroup difference according to the dose of SGLT2 inhibitors was not significant (Psubgroup0.05). SGLT2 inhibitors used at whether high dose or low dose are associated with the decreased risks of 12 cardiopulmonary disorders (eg, bradycardia, atrial fibrillation, hypertensive emergency, asthma, chronic obstructive pulmonary disease, and sleep apnea syndrome). These findings may suggest the potential efficacy of high- or low-dose SGLT2 inhibitors for the prevention and treatment of these cardiopulmonary disorders.

Spiroalanfurantones A-D (1-4), four eudesmanolide-furan sesquiterpene adducts with an unprecedented pentacyclic 6/6/5/5/5 skeleton, were isolated from the roots of Inula helenium. Their structures were elucidated by spectroscopic data analysis and single-crystal X-ray diffraction analysis. The plausible biosynthetic pathway for 1-4 is presented. Bioassay showed that compounds 1 and 2 significantly inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 17.3 and 9.5 μM, respectively.

Twenty-one eudesmane-type sesquiterpenes, including five new compounds, were isolated from the roots of Inula helenium. The structures of the new compounds (1–5) were determined by extensive spectroscopic data interpretation, single-crystal X-ray diffraction analysis and ECD calculations. Six compounds can synergistically enhance cisplatin effect against ovarian cancer cells, the structure − activity relationship for the synergistic effect of these compounds with cisplatin was revealed for the first time, which provides useful clues to develop novel sensitizers to overcome drug resistance in cancer. In addition, fifteen sesquiterpenes exhibited significant anti-inflammatory activity, which provided promising candidates for development of anti-inflammatory agent.

Spiroalanfurantones A-D (

Based on the equivalent circuit of the self-excited induction generator, an iterative method is proposed to predict the steady state performances by equating the loop impedance to zero. The proposed method is much simpler than Newton-Raphson method and optimization-based method. To facilitate the calculation, a simplified technique for reducing the orders of the equations is used. The fact that the calculated results coincide with those obtained experimentally shows the accuracy and validity of the proposed method. The effects of generator parameters on the external characteristics are studied. The simulation results indicate that the rotor resistance affects both the terminal voltage and frequency. The stator resistance, the stator leakage reactance and the rotor leakage reactance have no significant effect on the frequency

We present the two cases of men who were admitted to our hospital with effort angina and three vessels lesions. The symptoms were alleviated after three sirolimus-eluting stents implantation. But on the scheduled discharge day when the patients were on therapy of clopidogrel, in combination with aspirin or anticogulation, subacute stent thrombosis (SST) happened and led to patients' death.

The rapidly activating delayed rectifier potassium current (I(Kr)), whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene (hERG), is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K(+) current (I(hERG)).Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the I(hERG) before and after the exposure to arecoline.Arecoline decreased the amplitude and the density of the I(hERG) in a concentration-dependent manner (IC(50) = 9.55 mmol/L). At test potential of +60 mV, the magnitude of I(hERG) tail at test pulse of -40 mV was reduced from (151.7 ± 6.2) pA/pF to (84.4 ± 7.6) pA/pF (P0.01, n = 20) and the magnitude of I(hERG) tail at test pulse of -110 mV was reduced from (-187.5 ± 9.8) pA/pF to (-97.6 ± 12.6) pA/pF (P0.01, n = 20). The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of I(hERG) was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of I(hERG) by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse.Arecoline could potently block I(hERG) in both frequency and state-dependent manner.

To explore the effect of children-sized fibreoptic bronchoscope in improving the safety of whole-lung lavage (WLL).Patients from May 2006 to May 2010 using children-sized fibreoptic bronchoscope to assistant the location were assigned to fibreoptic bronchoscope group. Patients from May 1998 to Nov 2004 using traditional stethoscope to help intubation were assigned to control group. The adverse reactions and complications were compared.There were liquid leakage 1 case (0.96%), hypoxia 3 cases (2.88%) and liquid retained over 1000 ml 15 cases (14.42%) in fibreoptic bronchoscope group. In contrast, liquid leakage 24 cases (6.38%), hypoxia 42 cases (11.17%) and liquid retained over 1000 ml 135 cases (35.90%) happened in control group. The differences between the two groups were significant (P0.05, P0.01).Using children-sized fibreoptic bronchoscope in WLL can promote the situation of double-lumen tube, help separation the two lungs, decrease complications and improving safety.