A sensitive, high-throughput, and ecofriendly method for the determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin by supercritical fluid chromatography and tandem mass spectrometry.

A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC2 ™ BEH 2-EP column within 2.5 min by gradient elution using compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode. For sample preparation, 50 µL of the sample was processed by modified high-throughput, one-step protein precipitation using hydrogen peroxide as a stabilizer to protect the endoperoxide-containing artemisinin derivatives from degradation. The calibration curves were linear over the concentration range of 2.0-1000 ng/mL for both artemether and dihydroartemisinin, and 1.0-5000 ng/mL for lumefantrine. The values of selectivity, lower limit of quantification, linearity, accuracy, precision, matrix effects, stability, and recovery met the acceptable range according to the Food and Drug Administration guidelines. The developed method enables high resolution and speed as well as low cost, low solvent consumption, and short time and was successfully applied to pharmacokinetic studies through the intravenous administration of an artemether-lumefantrine lipid emulsion in rats.

Vertebral and carotid artery aneurysms and polyarthritis in a patient with Takayasu arteritis: A case report.

Takayasu arteritis (TA) is a common autoimmune disease in the clinical setting. However, vertebral artery aneurysms caused by TA are rarely reported. We herein describe a 28-year-old man with multiple vertebral artery aneurysms and carotid artery aneurysms caused by TA, which showed typical wall thickening and lumen dilation with a "string of beads" appearance by Doppler ultrasound and radiology. Previous studies have shown that most TA-associated vertebral artery lesions are stenosis, occlusion, and dissection of the intracranial part of the artery. In this case, TA mainly affected the cervical segment of the vertebral artery (the intracranial segment was not obviously involved), and the main manifestations were aneurysms and occlusion. This case provides more information for further understanding of TA-associated vertebral artery lesions.

Determinants of the heavily right-tailed residential housing price in Tianjin.

The housing price in Tianjin, one of the typical monocentric cities of China, exhibits a heavily right-tailed distribution even after the logarithm transformation of the price, which might lead to a biased estimation of the parameters under normal distribution assumption. Therefore, the extended Cox proportional hazards regression model and the generalized concept of relative risk are used to identify factors associated with the housing price. The analysis shows that the implementation dates of the macro regulation policies were related to the price changing trends. Qualities of public elementary and secondary schools were significantly associated with the housing price, and the associations between the structure and neighborhood characteristics and the housing price were influenced by the distance of the residential property to downtown Tianjin.

Simplifying Physiological Left Bundle Branch Area Pacing Using a New Nine-Partition Method.

BACKGROUND: Left bundle branch area pacing (LBBaP) is accepted as a physiological form of pacing; however, it is complex and usually requires an expensive electrophysiological recording system. METHODS: A simplified approach ("9-partition method") was explored to perform LBBaP. In this method, a right anterior oblique 30° fluoroscopic image of the ventricle was divided into 9 sections ("3 × 3" partitions). From May 2018 to February 2019, we enrolled 51 consecutive patients who underwent pacemaker implantation. The patients were nonrandomly allocated to either the conventional LBBaP (c-LBBaP) group or simplified LBBaP (s-LBBaP) group. RESULTS: The mean age was 68.53 ± 11.90 years, and 32 (62.7%) patients were male. The overall success rate was 90.2% (46/51). Compared with the c-LBBaP group, the s-LBBaP group had a significantly lower total procedure duration (91.57 ± 19.51 minutes vs 70.68 ± 13.26 minutes; P < 0.001) and fluoroscopy duration (16.52 ± 5.34 minutes vs 10.54 ± 3.13 minutes; P < 0.001). The time from the 3830 lead and sheath passage through the tricuspid valve to an acceptable initial fixation site (4.69 ± 1.61 minutes vs 2.75 ± 1.04 minutes; P < 0.001) and the time to the left bundle branch lead being implanted successfully (11.78 ± 3.00 minutes vs 7.67 ± 2.45 minutes; P < 0.001) for the c-LBBaP vs s-LBBaP groups, respectively, were significantly different. After 3 months, there were no significant differences in the capture threshold, R wave amplitude, impedance, or QRS duration between the groups. CONCLUSIONS: Compared with the c-LBBaP approach, our simplified 9-partition method was faster and did not require an expensive electrophysiological recording system.

Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance.

Mitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP+)-conjugated Brij 98 as the functional stabilizer to modify paclitaxel (PTX) nanocrystals (NCs) against drug-resistant cancer cells. Evaluations were performed on 2D monolayer and 3D multicellular spheroids (MCs) of MCF-7 cells and MCF-7/ADR cells. In comparison with free PTX and the non-targeted PTX NCs, the targeted PTX NCs showed the strongest cytotoxicity against both 2D MCF-7 and MCF-7/ADR cells, which was correlated with decreased mitochondrial membrane potential. The targeted PTX NCs exhibited deeper penetration on MCF-7 MCs and more significant growth inhibition on both MCF-7 and MCF-7/ADR MCs. The proposed strategy indicated that the TPP+-modified NCs represent a potentially viable approach for targeted chemotherapeutic molecules to mitochondria. This strategy might provide promising therapeutic outcomes to overcome MDR.

Immediate clinical outcomes of left bundle branch area pacing vs conventional right ventricular pacing.

BACKGROUND: Left bundle branch area pacing (LBBaP) is a new physiological pacing strategy that produces comparable clinical effects to His bundle pacing (HBP). OBJECTIVE: The purpose of this study was to investigate the immediate clinical outcomes of LBBaP vs RVP. METHODS AND RESULTS: From April 2018 to September 2018, we included 44 patients under continuous pacemaker implantation. Patients were randomly divided into the LBBaP group and conventional RVP group. Compared to the RVP group, the LBBaP group displayed significantly increased operative (90.10 ± 19.68 minutes vs 61.57 ± 6.62 minutes, P < .001) and X-ray exposure times (15.55 ± 5.62 minutes vs 4.67 ± 2.06 minutes, P < .001). The lead threshold of the LBBaP group was increased (0.68 ± 0.20 mV vs 0.51 ± 0.0 mV, P = .001), while the R-wave amplitude and ventricular impedance did not significantly differ between the two groups. The conventional RVP procedure significantly widened the QRS complex (93.62 ± 8.28 ms vs 135.19 ± 12.21 ms, P = .001), whereas the LBBaP had no effect on QRS complex (130.13 ± 43.30 ms vs 112.63 ± 12.14 ms, P = .904). Furthermore, the LBBaP procedure significantly narrowed the QRS complex in patients with left bundle branch block (LBBB) (168.43 ± 38.870 ms vs 119.86 ± 6.69 ms, P = .019). CONCLUSION: LBBaP is a new physiological, safe and effective pacing procedure with a high overall success rate. Compared to conventional RVP, LBBaP can correct LBBB, thereby improving cardiac electrical dyssynchrony.

Ultrasound Biomicroscopic Imaging for Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis and Markers of Inflammation in Atherosclerotic Development in Apolipoprotein-E Knockout Mice.

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis. We divided IL-1Ra(+/-)/apolipoprotein-E (apoE)(-/-) and IL-1Ra(+/+)/apoE(-/-) mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra(+/+)/apoE(+/+) mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and CRP were quantified in the 3 murine groups. At 16 weeks, plaque thickness in the ascending aortas of the IL-1Ra(+/-)/apoE(-/-) mice was significantly greater than that in the IL-1Ra(+/+)/apoE(-/-) mice, on ultrasound and histology (P <0.01). In contrast, at 32 weeks, the differences between these 2 genotypes were not statistically significant. Serum IL-1 levels were lower in the IL-1Ra(+/-)/apoE(-/-) mice than in the IL-1Ra(+/+)/apoE(-/-) mice at 16 and 32 weeks (P <0.05). At 16 weeks, serum CRP levels in the IL-1Ra(+/-)/apoE(-/-) mice were higher than in the IL-1Ra(+/+)/apoE(-/-) mice (P <0.01). Our results suggest that ultrasound biomicroscopy enables evaluation of atherosclerotic lesions in vivo, noninvasively and in real-time, in apoE(-/-) mice. Partial IL-1Ra deficiencies might promote early plaque development in 16-week-old apoE(-/-) mice. The balance of IL-1 and IL-1Ra might influence atherosclerotic development. Finally, CRP might affect the initiation of atherosclerosis, rather than its progression.

Giant aneurysm of right coronary artery fistula into left ventricle coexisting with noncompaction of left ventricular myocardium.

Coronary artery fistula (CAF) and noncompaction of the ventricular myocardium (NCVM) result from obliteration or compact failure of the intramyocardial trabecular sinusoids to form a ventricular cavity wall. The draining site of a right coronary artery (RCA) fistula may usually be the right ventricle, right atrium, or pulmonary artery. An RCA aneurysm with a fistula to the left ventricle is rare. We report a patient with an RCA aneurysm with a fistula to the left ventricle coexisting with NCVM. The patient's condition was diagnosed by echocardiography and contrast-enhanced multidetector computed tomography.

Intravenous leiomyomatosis with intracardiac extension: echocardiographic study and literature review.

Uterine leiomyomatosis is a common disease in women; however, intravenous leiomyomatosis with intracaval and intracardiac tumor extension is rare. We sought to analyze the clinical and echocardiographic features of intracardiac leiomyomatosis. From January 2003 through July 2012, 7 women (age range, 24-59 yr) underwent surgical resection of histopathologically diagnosed intracardiac leiomyomas at our hospital. Most of the patients had histories of hysterectomy or uterine leiomyoma. We retrospectively analyzed their preoperative echocardiograms. We found that the tumors had no stalks, did not adhere to the wall of the right side of the heart, were highly mobile, and moved back and forth in the right atrium near the tricuspid orifice. All tumors originated from the inferior vena cava and had borders well demarcated from that structure's wall. Most of the masses extended into the inferior vena cava and right atrium through the right internal and common iliac veins. Computed tomograms revealed pelvic tumors and contiguous filling defects in 6 patients. When echocardiograms reveal a right-sided cardiac mass that originates from the inferior vena cava, particularly in women who have a history of hysterectomy or uterine leiomyoma, intracardiac leiomyomatosis should be suspected. If the mass has no stalk and freely moves within the inferior vena cava and right-sided cardiac chambers without attachment to the endothelial surface or endocardium, intracardiac leiomyomatosis should be diagnosed. We discuss our findings and briefly review the relevant medical literature.

Ultrasound bio-microscopy for measurement of coronary artery flow and estimation of infarct size in a mouse model of acute myocardial infarction.

Ultrasound bio-microscopy was used to measure hemodynamic changes in the left main coronary artery after myocardial infarction (MI), and its usefulness in estimating infarct size was evaluated. MI was induced by left anterior descending artery ligation. Diastolic peak velocity (Vd), mean flow velocity (Vmean) and the velocity-time integral (VTI) were measured 2 and 6 h after MI. Serum troponin I levels were assayed 2, 6 and 12 h after MI. At 2 h, Vmean and VTI significantly differed between mice that underwent low and high left anterior descending artery ligation; Vd, Vmean and VTI were correlated with infarct size (r = -0.557, -0.693 and -0.672, respectively; all p < 0.01). Infarct size was more strongly correlated with 2-h ultrasound bio-microscopy measurements than with 2-h serum troponin I level. Measurement of coronary artery blood flow by ultrasound bio-microscopy may be useful for early estimation of infarct size in mice.