Relationship between epicardial fat volume on cardiac CT and atherosclerosis severity in three-vessel coronary artery disease: a single-center cross-sectional study.

BACKGROUND: The ideal treatment strategy for stable three-vessel coronary artery disease (CAD) patients are difficult to determine and for patients undergoing conservative treatment, imaging evidence of coronary atherosclerotic severity progression remains limited. Epicardial fat volume (EFV) on coronary CT angiography (CCTA) has been considered to be associated with coronary atherosclerosis. Therefore, this study aims to evaluate the relationship between EFV level and coronary atherosclerosis severity in three-vessel CAD. METHODS: This retrospective study enrolled 252 consecutive patients with three-vessel CAD and 252 normal control group participants who underwent CCTA between January 2018 and December 2019. A semi-automatic method was developed for EFV quantification on CCTA images, standardized by body surface area. Coronary atherosclerosis severity was evaluated and scored by the number of coronary arteries with ≥ 50% stenosis on coronary angiography. Patients were subdivided into groups on the basis of lesion severity: mild (score = 3 vessels, n = 85), moderate (3.5 vessels ≤ score < 4 vessels, n = 82), and severe (4 vessels ≤ score ≤ 7 vessels, n = 85). The independent sample t-test, analysis of variance, and logistic regression analysis were used to evaluate the associations between EFV level and severity of coronary atherosclerosis. RESULTS: Compared with normal controls, three-vessel CAD patients had significantly higher EFV level (65 ± 22 mL/m2 vs. 48 ± 19 mL/m2; P < 0.001). In patients with three-vessel CAD, there was a progressive decline in EFV level as the score of coronary atherosclerosis severity increased, especially in those patients with a body mass index (BMI) ≥ 25 kg/m2 (75 ± 21 mL/m2 vs. 72 ± 22 mL/m2 vs. 62 ± 17 mL/m2; P < 0.05). Multivariable regression analysis showed that both BMI (OR 3.40, 95% CI 2.00-5.78, P < 0.001) and the score of coronary atherosclerosis severity (OR 0.49, 95% CI 0.26-0.93, P < 0.05) were independently related to the change of EFV level. CONCLUSION: Three-vessel CAD patients do have higher EFV level than the normal controls. While, there may be an inverse relationship between EFV level and the severity of coronary atherosclerosis in patients with three-vessel CAD.

FAK inhibitors in cancer, a patent review - an update on progress.

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

Two single nucleotide polymorphisms in TSLP gene are associated with asthma susceptibility in Chinese Han population.

BACKGROUND: Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2(TH2) cells. Thymic stromal lymphopoietin (TSLP) can aggravate asthmatic lung inflammation by activating dendritic cells (DCs) to promote TH2 differentiation. TSLP promoter polymorphisms are associated with susceptibility to bronchial asthma in Japanese population. We sought to determine whether single nucleotide polymorphisms (SNPs) in TSLP gene are associated with asthma in Chinese Han population. OBJECTIVE: To analyze the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to evaluate the association between the two SNPs and asthma susceptibility in Chinese Han population by using case-control study. METHODS: five hundred and thirty one asthmatic patients and 540 age-sex matched normal controls were collected and DNA were extracted from peripheral blood, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were detected with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotype and allele frequencies were calculated and analyzed with Chi-square test. RESULTS: Frequencies of CC/CT/TT genotypes at Rs2289276 site were 0.4706/0.4392/0.0902 in the asthmatic patients and 0.5604/0.3800/0.0595 in the healthy controls. Frequencies of CC/CG/GG genotypes at Rs2289278 site were 0.6502/0.2966/0.0532 in the asthmatic patients and 0.5795/0.3428/0.0777 in the healthy controls. The genotype and allele frequencies of the two SNPs in asthma patients were significantly different from those in the healthy controls. Rs2289278 C allele was correlated with decreased FEV(1): FVC (P ≤ .05). CONCLUSIONS: TSLP variants are significantly associated with bronchial asthma. TSLP might be a new therapeutic target molecule for asthma.

Comparison of Regression Analysis and Transfer Function in Estimating the Parameters of Central Pulse Waves from Brachial Pulse Wave.

This study analyzed ascending branch slope (A_slope), dicrotic notch height (Hn), diastolic area (Ad) and systolic area (As) diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), subendocardial viability ratio (SEVR), waveform parameter (k), stroke volume (SV), cardiac output (CO), and peripheral resistance (RS) of central pulse wave invasively and non-invasively measured. Invasively measured parameters were compared with parameters measured from brachial pulse waves by regression model and transfer function model. Accuracy of parameters estimated by regression and transfer function model, was compared too. Findings showed that k value, central pulse wave and brachial pulse wave parameters invasively measured, correlated positively. Regression model parameters including A_slope, DBP, SEVR, and transfer function model parameters had good consistency with parameters invasively measured. They had same effect of consistency. SBP, PP, SV, and CO could be calculated through the regression model, but their accuracies were worse than that of transfer function model.

Regression analysis and transfer function in estimating the parameters of central pulse waves from brachial pulse wave.

This study mainly analyzed the parameters such as ascending branch slope (A_slope), dicrotic notch height (Hn), diastolic area (Ad) and systolic area (As) diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), subendocardial viability ratio (SEVR), waveform parameter (k), stroke volume (SV), cardiac output (CO) and peripheral resistance (RS) of central pulse wave invasively and non-invasively measured. These parameters extracted from the central pulse wave invasively measured were compared with the parameters measured from the brachial pulse waves by a regression model and a transfer function model. The accuracy of the parameters which were estimated by the regression model and the transfer function model was compared too. Our findings showed that in addition to the k value, the above parameters of the central pulse wave and the brachial pulse wave invasively measured had positive correlation. Both the regression model parameters including A_slope, DBP, SEVR and the transfer function model parameters had good consistency with the parameters invasively measured, and they had the same effect of consistency. The regression equations of the three parameters were expressed by Y'=a+bx. The SBP, PP, SV, CO of central pulse wave could be calculated through the regression model, but their accuracies were worse than that of transfer function model.

Antiosteoporotic activity and constituents of Podocarpium podocarpum.

Our study aimed to investigate the antiosteoporotic properties of the ethanol extract of Podocarpium podocarpum (DC.) Yang et Huang (PE) in ovariectomized (OVX) rats and to characterize the active constituents. As a result, PE significantly inhibited the increased urinary Ca excretion and activity of bone resorption markers including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline crosslinks and cathepsin K in OVX rats, whereas exhibited little effects on the body, uterus and vagina weight. Detailed micro-CT analysis showed that PE notably enhanced bone quality, with increased bone mineral content (BMC), bone volume fraction (BVF), connectivity density (CD), tissue mineral content (TMC), tissue mineral density (TMD) and trabecular number (Tb. N), and decreased trabecular separation (Tb. Sp), in OVX animal. Those findings implied that PE had notable antiosteoporotic effect, especially effective in preventing bone resorption, with little side-effects on reproductive tissue. Further chemical investigation led to the isolation of 17 flavonoids, most of which showed significantly stimulatory effect on osteoblastic proliferation, ALP activity and mineralized nodes formation as well as inhibitory effect on osteoclastic TRAP activity in osteoblastic and osteoclastic cells. Our results indicated that PE, with abundant flavonoids, had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis induced by estrogen deficiency through herbal remedy.

[Subcellular distribution and chemical forms of Cd and Zn in Sedum jinianum].

With water culture and by using differential centrifugation technique and sequential extraction, the subcellular distribution and chemical forms of Cd and Zn in the root, stem and leaf of Sedum jinianum were studied. In treatment 10 micromol Cd x L(-1), most of Cd in S. jinianum was in the soluble fraction of cell; while in treatment 100 miromol Cd x L(-1), the Cd in root was mainly deposited on cell wall, the Cd in stem was mainly on cell wall and in soluble fraction, and over 90% of Cd in leaf were in soluble fraction. In treatment 100 micromol Cd x L(-1), the proportion of Cd on the cell walls of root, stem and leaf increased, while that in soluble fraction decreased. In treatments 1 and 800 micromol Zn x L(-1), the Zn in root, stem and leaf mainly presented in soluble fraction; while in treatments with the Zn level between 1.0 and 800 micromol x L(-1), there were no differences in the proportions of Zn in the soluble fraction and on the cell walls of root, stem and leaf. Very low proportions of Cd and Zn were found in cell organelle. The Cd in the root, stem and leaf was predominated with NaCl- and water-extractable forms, while Zn in the plants were existed in numerous chemical forms.