The accuracy and influencing factors of Doppler echocardiography in estimating pulmonary artery systolic pressure: comparison with right heart catheterization: a retrospective cross-sectional study.

BACKGROUND: Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO) has been widely adopted to screen for pulmonary hypertension (PH), but there is still a high proportion of overestimation or underestimation of sPAPECHO. We therefore aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as a reference. METHODS: A total of 218 highly suspected PH patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR)-related methods and RHC results were tested by Pearson and Bland-Altman methods. TR-related methods included peak velocity of TR (TR Vmax), TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure (mPAPECHO), and sPAPECHO. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, the ROC curve was used to compare the diagnostic efficacy of sPAPECHO with other TR-derived parameters. The ratio (sPAPECHO-sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between - 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than - 10% were classified as the underestimated group. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis. RESULTS: sPAPECHO had the highest correlation coefficient (r = 0.781, P < 0.001), best diagnostic efficiency (AUC = 0.98), and lowest bias (mean bias = 0.07 mm Hg; 95% limits of agreement, - 32.08 to + 32.22 mm Hg) compared with other TR-related methods. Ordinal regression analysis showed that TR signal quality, sPAPRHC level, and pulmonary artery wedge pressure (PAWP) affected the accuracy of sPAPECHO (P < 0.05). Relative to the good signal quality, the OR values of medium and poor signal quality were 0.26 (95% CI: 0.14, 0.48) and 0.23 (95% CI: 0.07, 0.73), respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56 (95% CI: 9.57, 48.55) and 5.13 (95% CI: 2.55, 10.32), respectively. The OR value of PAWP was 0.94 (95% CI: 0.89, 0.99). TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO. CONCLUSIONS: In this study, we found that all TR-related methods, including sPAPECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.

Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review.

Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors.

Intestinal mucosal barrier in functional constipation: Dose it change?

BACKGROUND: The intestinal mucosal barrier is the first line of defense against numerous harmful substances, and it contributes to the maintenance of intestinal homeostasis. Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases. However, no study thoroughly evaluated this barrier in patients with functional constipation (FC). AIM: To investigate the intestinal mucosal barrier in FC, including the mucus barrier, intercellular junctions, mucosal immunity and gut permeability. METHODS: Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital. The colonic mucus barrier, intercellular junctions in the colonic epithelium, mucosal immune state and gut permeability in FC patients were comprehensively examined. Goblet cells were stained with Alcian Blue/Periodic acid Schiff (AB/PAS) and counted. The ultrastructure of intercellular junctional complexes was observed under an electron microscope. Occludin and zonula occludens-1 (ZO-1) in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction. Colonic CD3+ intraepithelial lymphocytes (IELs) and CD3+ lymphocytes in the lamina propria were identified and counted using immunofluorescence. The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay. RESULTS: Compared to healthy controls, the staining of mucus secreted by goblet cells was darker in FC patients, and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients (control, 18.67 ± 2.99; FC, 22.42 ± 4.09; P = 0.001). The intercellular junctional complexes in the colonic epithelium were integral in FC patients. The distribution of mucosal occludin and ZO-1 was not altered in FC patients. No significant differences were found in occludin (control, 5.76E-2 ± 1.62E-2; FC, 5.17E-2 ± 1.80E-2; P = 0.240) and ZO-1 (control, 2.29E-2 ± 0.93E-2; FC, 2.68E-2 ± 1.60E-2; P = 0.333) protein expression between the two groups. The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls (P = 0.145, P = 0.451, respectively). No significant differences were observed in the number of CD3+ IELs per 100 epithelial cells (control, 5.62 ± 2.06; FC, 4.50 ± 2.16; P = 0.070) and CD3+ lamina propria lymphocytes (control, 19.69 ± 6.04/mm2; FC, 22.70 ± 11.38/mm2; P = 0.273). There were no significant differences in serum D-lactic acid [control, 5.21 (4.46, 5.49) mmol/L; FC, 4.63 (4.31, 5.42) mmol/L; P = 0.112] or zonulin [control, 1.36 (0.53, 2.15) ng/mL; FC, 0.94 (0.47, 1.56) ng/mL; P = 0.185] levels between FC patients and healthy controls. CONCLUSION: The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.

A simpler noninvasive method of predicting markedly elevated pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension.

Several echocardiographic methods to estimate pulmonary vascular resistance (PVR) have been proposed. So far, most studies have focused on relatively low PVR in patients with a nonspecific type of pulmonary hypertension. We aimed to clarify the clinical usefulness of a new echocardiographic index for evaluating markedly elevated PVR in chronic thromboembolic pulmonary hypertension (CTEPH). We studied 127 CTEPH patients. We estimated the systolic and mean pulmonary artery pressure using echocardiography (sPAPEcho, mPAPEcho) and measured the left ventricular internal diameter at end diastole (LVIDd). sPAPEcho/LVIDd and mPAPEcho/LVIDd were then correlated with invasive PVR. Using receiver operating characteristic curve analysis, a cutoff value for the index was generated to identify patients with PVR > 1000 dyn·s·cm-5. We analyzed pre- and postoperative hemodynamics and echocardiographic data in 49 patients who underwent pulmonary endarterectomy (PEA). In this study, mPAPEcho/LVIDd moderately correlated with PVR (r = 0.51, p < 0.0001). There was a better correlation between PVR and sPAPEcho/LVIDd (r = 0.61, p < 0.0001). sPAPEcho/LVIDd ≥ 1.94 had an 77.1% sensitivity and 75.4% specificity to determine PVR > 1000 dyn·s·cm-5 (area under curve = 0.804, p < 0.0001, 95% confidence interval [CI], 0.66-0.90). DeLong's method showed there was a statistically significant difference between sPAPEcho/LVIDd with tricuspid regurgitation velocity2/velocity-time integral of the right ventricular outflow tract (difference between areas 0.14, 95% CI, 0.00-0.27). The sPAPEcho/LVIDd and mPAPEcho/LVIDd significantly decreased after PEA (both p < 0.0001). The sPAPEcho/LVIDd and mPAPEcho/LVIDd reduction rate (ΔsPAPEcho/LVIDd and ΔmPAPEcho/LVIDd) was significantly correlated with PVR reduction rate (ΔPVR), respectively (r = 0.58, p < 0.01; r = 0.69, p < 0.05). In conclusion, the index of sPAPEcho/LVIDd could be a simpler and reliable method in estimating CTEPH with markedly elevated PVR and also be a convenient method of estimating PVR both before and after PEA.

Flavones and Lignans from the Stems of Wikstroemia scytophylla Diels.

BACKGROUND: The genus Wikstroemia has about 70 species, but only a limited number of species have been studied chemically. Wikstroemia indica has long been used as a traditional crude drug in China. However, there is no report about the bioactivity of Wikstroemia scytophylla. OBJECTIVE: This paper reports the chemical investigation and biological evaluation of the W. scytophylla. MATERIALS AND METHODS: The EtOAc extraction of W. scytophylla was isolated using chromatographic methods, and the compounds were analyzed by spectroscopic methods. The in vitro antitumor activities against five human cancer cell lines were performed according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS: The chemical investigation of the stems of W. scytophylla resulted in the isolation of 12 compounds mainly including one biflavone (1), five flavones (2-6) compounds, and six lignans (7-12), in which compound 8 was a new natural product. Compounds 1 and 7-12 were evaluated for their antitumor activities while these compounds showed weak cytotoxicity with the half maximal inhibitory (IC50) values more than 40 µM. CONCLUSION: All of these compounds were isolated from this plant for the first time, and compounds 2-12 were first reported from genus Wikstroemia, in which compound 8 was a new natural product. Compounds 1 and 7-12 exhibited weak antitumor activities (IC50>40 µM). The chemotaxonomic significance of all the isolations was summarized. SUMMARY: The chemical investigation of the stems of W. scytophylla resulted in the isolation of 12 compoundsThe 12 compounds including six lignans (7-12), in which compound 8 was a new natural productThe isolated compounds 1 and 7-12 were evaluated for their antitumor activitiesThe chemotaxonomic significance of all the isolations was summarized. Abbreviations used: MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; IC50: Half maximal inhibitory; HL-60: Human leukemia cell line; SMMC-7721: Human hepatocellular carcinoma cell line; A549: Human lung tumor cell line; MCF-7: Human breast cancer cell line; SW480: Human colon cancer cell line; MS: Mass spectrometry; NMR: Nuclear Magnetic Resonance.

A new phenolic glycoside from Lindera nacusua.

The present study was designed to investigate the chemical constituents of Lindera nacusua and their antitumor activities. A new phenolic glycoside, namely 1-O-3-hydroxyphenyl-5-methoxyphenol-(6'-O-vanilloyl)-ß-d-glucopyranoside (1), together with five known phenolic glycosides (2-6), two anthraquinones (7, 8) and two γ-butanolides (9, 10), was isolated, and its structure was elucidated by spectroscopic and chemical methods. Compounds 1-10 were screened for their in vitro cytotoxicities against HL-60, SMMC-7721, A549, MCF-3 and SW480 cell lines by the MTS method. Compounds 9 and 10 showed moderate cytotoxicities with IC50 values ranging from 17.40 to 35.21 µM.