Diagnostic Accuracy of MRI for Detecting Cervical Invasion in Patients with Endometrial Carcinoma: A Meta-Analysis.

Objectives: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in the preoperative assessment of cervical invasion and to analyse the influence of different imaging protocols in patients with endometrial carcinoma. Methods: An extensive search of articles about MRI for assessing cervical invasion in patients with endometrial carcinoma was performed on PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials from January 2000 to July 2020. Two reviewers independently evaluated the methodological quality of each study by using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Diagnostic accuracy results and additional useful information were extracted. The pooled estimation data was obtained by statistical analysis. Results: A total of 42 eligible studies were included in the meta-analysis. Significant evidence of heterogeneity was found for detecting cervical invasion (I2 = 74.1%, P = 0.00 for sensitivity and I2 = 56.2%, P = 0.00 for specificity). The pooled sensitivity and specificity of MRI were 0.58 and 0.95 respectively. The use of higher field strength (3.0 T) demonstrated higher pooled sensitivity (0.74). Using diffusion weighted imaging (DWI) alone presented higher pooled sensitivity (0.86) than using other sequences. The studies that used dynamic contrast-enhanced MRI (DCE-MRI) alone showed higher sensitivity (0.80) and specificity (0.96) than those that used T2-weighted imaging (T2WI) alone. Conclusions: MRI shows high specificity for detecting cervical infiltration in endometrial carcinoma. Using DWI or a 3.0-T device may improve the pooled sensitivity. DCE-MRI demonstrates higher pooled sensitivity and specificity than T2WI.

Anti-hypertensive efficacy of amlodipine dosing during morning versus evening: A meta-analysis.

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.

Clutter and Range Ambiguity Suppression Using Diverse Pulse Train in Pulse Doppler System.

Pulse Doppler (PD) systems are widely used for moving target detection, especially in scenarios with clutter. Range ambiguity, which arises from fixed parameters in waveforms, is an inherent drawback in conventional systems. By using a diverse pulse train such as a train of coherent diverse phase coded pulses, these ambiguous peaks can be suppressed effectively but at the cost of sidelobe dispersions. In this work, a novel efficient PD process is proposed to suppress range ambiguity and detect moving targets under strong clutter. Poly-phase coded pulses are employed along with optimal receiving filters, by which the dispersed sidelobes are mitigated to a great extent. Moreover, a novel clutter suppression procedure is included in the PD process, by which strong clutter can be greatly suppressed. Well-designed receiving and inverse filters are employed. Simulation examples are presented to verify the theories. Compared with conventional methods, much better detection results are obtained for both near and remote targets, especially in scenarios with strong clutter.

Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors.

A series of 4-(2-fluorophenoxy)quinoline derivatives containing an acylhydrazone moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and five cancer cell lines (A549, H460, HT-29, MKN-45, and U87MG). Most compounds showed weak to excellent antiproliferative activity. The most promising analog, 40 (c-Met IC50 = 1.86 nM), displayed 1.3-, 6.8-, 1.5-, 3.5-fold increase against HT-29, H460, A549 and U87MG cell lines, respectively, compared with Foretinib. An analysis of structure-activity relationships revealed that an acylhydrazone scaffold with an unsubstituted sp(2) hybridized carbon adjacent to the 4-CF3 phenyl ring is favorable for antitumor activity.

Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents.

Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50=2.20nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14µM, 0.18µM, 0.09µM, 0.03µM, and 1.06µM against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively.

Design, synthesis and structure-activity relationships of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety as potential antitumor agents.

A series of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety were synthesized and evaluated for their in vitro cytotoxic activity against five cancer cell lines (HT-29, H460, A549, MKN-45, and U87MG). Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines. Compounds 15a, 20a, 15b, 15c, 20d, and 16e were further examined for their inhibitory activity against c-Met kinase. The most promising compound 15a (c-Met half-maximal inhibitory concentration [IC50] = 2.15 nM) showed remarkable cytotoxicity against HT-29, H460, and A549 cell lines with IC50 values of 0.10 µM, 0.13 µM, and 0.05 µM, respectively, and thus it was 1.5- to 2.3-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.

Design, synthesis and antitumor activity of novel artemisinin derivatives using hybrid approach.

In an attempt to develop potent and selective anti-tumor agents, two novel series of artemisinin-chalcone hybrids were designed, synthesized and screened for their antitumor activities against HT-29, A549, MDA-MB-231, HeLa and H460 cell lines in vitro. Nearly all of the tested compounds showed significantly increased anti-tumor activity compared with the corresponding dihydroartemisinin (DHA). Most of the title compounds displayed good selectivity toward HT-29 and HeLa cell lines with IC50 values ranging from 0.09 to 0.85 µM. Among them, the most promising compound 9c (IC50) range of 0.09-0.93 µM) was 10.5- to 70-times more active than DHA (IC50 range of 5.6-15.6 µM) respectively.

Synthesis and anti-proliferative in-vitro activity of two natural dihydrostilbenes and their analogues.

A total synthetic route for two natural dihydrostilbenes with significant cytotoxicity toward human cancer cell lines, (3-(2-(7-methoxybenzo[d][1,3]dioxol-5-yl)ethyl)phenol 1a and 6-(3-hydroxyphenethyl)benzo[d][1,3]dioxol-4-ol 1b), which were isolated from Bulbophyllum odoratissimum Lindl, was developed via Wittig-Horner reaction. The natural products 1a and 1b were obtained in 28% and 20% overall yield, respectively. Additionally, nine analogues, 1c-1k, of the two natural dihydrostilbenes were synthesized and evaluated for their anti-proliferative activity against human SGC-7901, KB and HT-1080 cell lines by MTT assay. The activities of 1c and 1d were in the same range as those of the natural products 1a and 1b.

Antidepressant-like effects of sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae).

The aim of this study was to investigate the effects of sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae) on the forced swimming test, and the central noradrenergic, dopaminergic and serotonergic activities in mice. Our results showed that sarsasapogenin treatment at 12.5, 25 and 50 mg/kg (p.o.) for 14 d significantly reduced the duration of immobility in the forced swimming test. These doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical assays showed that sarsasapogenin produced a marked increase of noradrenaline and serotonin levels at 50 mg/kg in both the hypothalamus and the hippocampus. Moreover, sarsasapogenin showed a monoamine oxidase inhibitory activity in the mouse brain. These findings suggest that the antidepressant activity of sarsasapogenin may involve the central monoaminergic neurotransmitter systems.

Solid lipid nanoparticles for enhancing vinpocetine's oral bioavailability.

An ultrasonic-solvent emulsification technique was adopted to prepare vinpocetine loaded Glyceryl monostearate (GMS) nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 50 degrees C, and in order to prepare nanoparticle using an ultrasonic-solvent emulsification technique. The mean particle size and droplet size distribution, drug loading capacity, drug entrapment efficiency (EE%), zeta potential, and long-term physical stability of the SLNs were investigated in detail respectively. Drug release from two sorts of VIN-SLN was studied using a dialysis bag method. A pharmacokinetic study was conducted in male rats after oral administration of 10 mg kg(-1) VIN in different formulations, it was found that the relative bioavailability of VIN in SLNs was significantly increased compared with that of the VIN solution. The amount of surfactant also had a marked effect on the oral absorption of VIN with SLN formulations. The absorption mechanism of the SLN formulations was also discussed. These results indicated that VIN absorption is enhanced significantly by employing SLN formulations. SLNs offer a new approach to improve the oral bioavailability of poorly soluble drugs.

Synthesis and anti-inflammatory activity of resveratrol analogs.

Seventeen novel resveratrol derivatives were synthesized. Their anti-inflammatory activities were tested on xylene-induced mouse ear edema. The pharmacological results showed that some compounds have potent anti-inflammatory activities.