The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer.

To determine whether ultrasound (US) features of breast cancer are associated with Breast Imaging and Reporting Data System molecular subtype, histologic grade, and hormone receptor status as well as to assess the predictive value of these features. Retrospective analysis of the medical records of 220 consecutive patients with invasive breast cancer was reviewed according to the PIK3CA-mutated molecular tumor subtype. US findings of all patients were analyzed. Breast tumors harboring a PIK3CA-mutation were large and exhibited liquefied necrosis and posterior echo attenuation in the nodule. Moreover, such tumors were lobulated and calcified. The aspect ratio of the PIK3CA-mutant was more likely >1. The average nodule elasticity (7.479 ± 0.993 m/s) was measured using US shear wave elastography. Microcalcification was easier to detect inside the nodule using a fluorescence technique. Measurement of the nodule blood flow spectrum showed that the internal blood flow resistance index of nodules was lower than that of other types of breast cancer. The sonographic features of PIK3CA-mutated breast cancers were strongly associated with extensive and liquefied necrosis. The ability to predict molecular subtypes, particularly using US to detect the triple-negative subtype, may play an important role in early management and treatment.

Synthesis, and anti-inflammatory activities of gentiopicroside derivatives.

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Quantitative evaluation and significance of ultrasound in bronchoalveolar lavage for lung consolidation in children with severe mycoplasma pneumonia.

BACKGROUND: The aim of this study was to evaluate the effect of lung ultrasound on bronchoalveolar lavage in the treatment of mycoplasma pneumonia in children. METHODS: Thirty children with mycoplasma pneumonia who were treated with medication and bronchial lavage were selected. We collected the results of laboratory and imaging examinations after admission, and the changes in lung consolidation area were examined by ultrasound before, immediately upon completion, and at 1, 3, and 7 days after bronchoalveolar lavage. The effective factors affecting bronchial lavage were analyzed through logistic regression. RESULTS: Univariate regression analysis showed significant differences in the lung consolidation area at admission, before, immediately upon completion, and at 1 and 7 days after lavage, as well as in the disease course and atelectasis (or not). Multivariate analysis showed that there were statistical differences in the lung consolidation area at admission, atelectasis (or not), and disease course: lung consolidation area at admission [odds ratio (OR): 2.31512, 95% confidence interval (CI): (0.00182, 0.031775), P=0.029474], atelectasis [OR: 2.695742, 95% CI: (0.079281, 0.597218), P=0.012629], and disease course [OR: -2.43347, 95% CI: (-0.02568, -0.00211), P=0.022773]. CONCLUSIONS: Lung ultrasound can evaluate the effect of bronchial lavage through lung consolidation and atelectasis, which can provide a reference for clinical treatment.

Application of lung ultrasonography in critically ill patients with COVID-19.

PURPOSE: Lung ultrasonography (LU) is useful to assess lung lesions and variations at bedside. To investigate the results of LU in severe and critical patients with coronavirus disease 2019 (COVID-19), we performed a single-institution study to evaluate the related lung lesions and variations, and prophylactic strategies, in a large referral and treatment center. METHODS: We included 91 adult patients with severe and critical COVID-19, namely 62 males and 29 females, with an average age of 59 ± 11 years, who underwent LU. We collected the following patient information: sex, age, days in hospital, and days in ICU. In the ultrasound examinations, we recorded the presence of discrete B lines, confluent B lines, consolidation, pleural thickening, pleural effusion, and pneumothorax (PTX). RESULTS: Among the 91 severe and critical patients, 59 cases had scattered B lines, 56 cases had confluent B lines, 58 cases had alveolar-interstitial syndrome (AIS), 48 cases had lung consolidation, six cases had pleural thickening, 39 cases had pleural effusion (average depth of the pleural effusion: 1.0 ± 1.5 cm), and 20 patients developed PTX. In the Cox multivariate analysis, there were significant differences in age, hospitalization days, ICU days, and lung consolidation. CONCLUSION: Lung ultrasonography performed at the bedside can detect lung diseases, such as B lines, PTX, pulmonary edema, lung consolidation, pleural effusion, and variations of these findings. Our findings support the use of LU and measurements for estimating factors, and monitoring response to therapy in severe and critical COVID-19 patients.

Exploring stereoselective excretion and metabolism studies of novel 2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid enantiomers.

R-/S-2-(2-Hydroxypropanamido)-5-trifluoromethyl benzoic acid (R-/S-HFBA), as a novel COX inhibitor, was firstly reported to have remarkable anti-inflammatory and antiplatelet aggregation activities by our group. In our previous study, stereoselective differences in pharmacokinetics were found between HFBA enantiomers after oral and intravenous administration of each enantiomer to rats. The discrepancies might be associated with the excretion and metabolism of the two enantiomers. In this research, an UHPLC-MS/MS method was established and validated for quantification of R-/S-HFBA in rats urine, feces and bile samples in excretion study. Moreover, an ultra high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) method was employed to understand the metabolism of R-/S-HFBA in rats. Results showed that the total cumulative excretion of R-/S-HFBA in three routes were 65.8% and 58.5% of the dose, respectively. The urinary excretion of R-/S-HFBA was the main route, which accounted for 40.2% and 31.7% respectively; the cumulative biliary excretion of R-/S-HFBA were 11.3% and 7.4%; the cumulative amounts of R-/S-HFBA excreted directly via feces without absorption from the gastrointestinal tract were 14.3% and 19.4%, respectively. R-/S-HFBA existed stereoselective discrepancy in excretion. In addition, 8 metabolites of S-HFBA were detected and tentatively identified including glucuronidation, glycine and N-acetyl conjugation while R-HFBA existed 7 metabolites without glycine conjugation. Formation of metabolites of R-/S-HFBA also exhibited stereoselectivity. In summary, these new findings on excretion and metabolism of R-/S-HFBA provided valuable information for stereoselective pharmacokinetics and were greatly helpful for further investigation, such as safety and mechanism of action.

Rauvomines A and B, Two Monoterpenoid Indole Alkaloids from Rauvolfia vomitoria.

Two unusual normonoterpenoid indole alkaloids rauvomine A (1) and rauvomine B (2), together with two known compounds peraksine (3) and alstoyunine A (4), were isolated from the aerial parts of Rauvolfia vomitoria. The structures with absolute configurations of 1 and 2 were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 is a novel C18 normonoterpenoid indole alkaloid with a substituted cyclopropane ring that forms an unusual 6/5/6/6/3/5 hexcyclic rearranged ring system. The plausible biogenetic pathways of 1 and 2 were proposed. Compound 2 exhibited significant anti-inflammatory activity.

Anesthetic constituents of Zanthoxylum bungeanum Maxim.: A pharmacokinetic study.

A sensitive and selective ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for the simultaneous determination of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-γ-sanshool in rat plasma after the subcutaneous and intravenous administration of an extract of the pericarp of Zanthoxylum bungeanum Maxim. Piperine was used as the internal standard. The analytes were extracted from rat plasma by liquid-liquid extraction with ethyl acetate and separated on a Thermo Hypersil GOLD C18 column (2.1 mm × 50 mm, 1.9 µm) with a gradient elution system at a flow rate of 0.4 mL/min. The mobile phase consisted of acetonitrile/0.05% formic acid in water and the total analysis time was 4 min. Positive electrospray ionization was performed using multiple reaction monitoring mode for the analytes. The calibration curves of the three analytes were linear over the tested concentration range. The intra- and interday precision was no more than 13.6%. Extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The developed and validated method was suitable for the quantification of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-γ-sanshool and successfully applied to a pharmacokinetic study of these analytes after subcutaneous and intravenous administration to rats.