The structural composition of components contributes to the superiority of the geoherb Alisma orientale for "diuresis and diffusing dampness".

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale. The effects of "diuresis and diffusing dampness" using salt-made Alisma orientale from seven different origins were investigated through pharmacodynamic experiments in vivo and in vitro. The results indicated that salt-made Alisma orientale from different origins had diuretic efficacy; this was demonstrated by the significant increase in the volume of rat urine, the concentration of Na+, K+, and Cl- in the urine, and the significant decrease in the levels of AQP-2 in rat renal medulla and HK-2 cells. It was also revealed that the diuretic effect of salt-made Alisma orientale from Fujian Province is stronger than those from other provinces. Moreover, the main components and their proportions in the salt-made Alisma orientale samples were further analyzed via principal component analysis. The results showed that alisol A 24-acetate, alisol B, and 23-acetyl alisol B are the main components of salt-made Alisma orientale, and the optimal structural ratio of alisol A 24-acetate, alisol B, and 23-acetyl alisol B was found to be 5.38 : 14.34 : 11.31 via optimizing the ratios of the three main components. It is worth noting that the optimal ratio of the three main components after optimization is the closest to the ratio of the three main components in salt-made Alisma orientale from Fujian Province. This paper reveals the "mystery" of the content ratio of the main active components and its effect on the efficacy, and showed that the proportional relationship between the content of multiple components is the key to their interactions. Therefore, this method of evaluating the quality of salt-made Alisma orientale is obviously reliable, and this study lays the foundations for quality evaluation of salt-made Alisma orientale and other herb slices.

[Study on synergistic anti-tumor effect of Shuangdan Capsules combined with 5-FU on hepatocellular carcinoma cells Huh-7 and xenograft mice].

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 µmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.

A multivariable model of BRAFV600E and ultrasonographic features for predicting the risk of central lymph node metastasis in cN0 papillary thyroid microcarcinoma.

Background: Prophylactic central lymph node dissection (CLND) in papillary thyroid microcarcinoma (PTMC) patients without clinical evidence of central lymph node metastasis (CLNM) remains controversial. The purpose of our study is to identify preoperative predictive factors for finding CLNM in Chinese PTMC patients, which may allow tailored CLND. Methods: We retrospectively reviewed 182 consecutive Chinese PMTC patients with negative central lymph nodes who underwent total thyroidectomy plus central neck dissection from October 2015 to December 2017. Chi-squared and multivariate analysis were performed to evaluate the association of CLNM with ultrasonographic and clinicopathologic characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the utility of markers in predicting CLNM. Results: The CLNM was found in 39.0% (71 of 182) of cN0 PTMC patients. In multivariate analysis, tumor size>7 mm (OR: 3.636, 95% CI: 1.671-7.914), marked hypoechogenicity (OR: 2.686, 95% CI: 1.080-6.678), multifocality (OR: 4.184, 95% CI: 1.707-10.258) and BRAFV600E mutation (OR: 5.339, 95% CI: 2.529-11.272) were independent predictors of CLNM. In ROC analysis integrating these predictors, the sensitivity was 63.4% and specificity was 80.2%, and the area under the ROC (AUC) was 0.755. Conclusion: In conclusion, we found tumor size>7 mm, marked hypoechogenicity, multifocality, and BRAFV600E mutation were risk factors for CLNM. In term of these preoperative risk factors for CLNM, prophylactic CLND should be cautiously performed in cN0 PTMC patients.

High BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma increases diagnostic efficacy in cytologically indeterminate thyroid nodules.

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.

[4, 8-disubstituted-8, 9-dihydro-pyrazine[2,3-g]quinazoline-7(6H)-ketones: a novel class of antitumor agents].

OBJECTIVE: To evaluate the antitumor activity of a novel class of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones in vitro, and to screen potential anticancer compounds for further study. METHODS: Seventeen compounds of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones were synthesized with solid-phase method for biological evaluation of EGFR tyrosine kinase. MTT method was used to evaluate the cytotoxic activity in vitro against three human cancer cell lines (human lung carcinoma cell line A549, human leukemia cell lines K562 and human gastric carcinoma cell line SGC7901). RESULTS: Compound 7-13 and 7-14 showed potent antitumor activities against A549 cells, with IC(50) values of 8.10 and 8.12 mol/L, respectively. Eight compounds showed proliferative inhibition effect on K562 cells, especially 7-2, 7-13 and 7-17, with IC(50) values of 2.22,0.57 and 7.20 mol/L,respectively.And compound 7-13 and 7-3 showed potent antitumor activity against SGC7901 cells, with IC(50) values of 4.20 and 9.71 mol/L, respectively. CONCLUSION: The synthesized compounds 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g] quinazoline-7(6H)-ketones show inhibition effects on human cancer cell lines in vitro. Compound 7-13 has anticancer activity in all three cancer cell lines, which might be used as a potential antitumor drug for further study.