Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase / 药物分析学报

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

Clinical application of free/total PSA ratio in the diagnosis of prostate cancer in men over 50 years of age with total PSA levels of 2.0-25.0 ng ml-1 in Western China / 亚洲男科学杂志(英文版)

The goal of this study was to investigate the clinical application of free/total prostate-specific antigen (F/T PSA) ratio, considering the new broad serum total PSA (T-PSA) "gray zone" of 2.0-25.0 ng ml-1 in differential diagnosis of prostate cancer (PCa) and benign prostate diseases (BPD) in men over 50 years in Western China. A total of 1655 patients were included, 528 with PCa and 1127 with BPD. Serum T-PSA, free PSA (F-PSA), and F/T PSA ratio were analyzed. Receiver operating characteristic curves were used to assess the efficiency of PSA and F/T PSA ratio. There were 47.4% of cancer patients with T-PSA of 2.0-25.0 ng ml-1. When T-PSA was 2.0-4.0 ng ml-1, 4.0-10.0 ng ml-1, and 10.0-25.0 ng ml-1, the area under the curve (AUC) of F/T PSA ratio was 0.749, 0.769, and 0.761, respectively. The best AUC of F/T PSA ratio was 0.811 when T-PSA was 2.0-25.0 ng ml-1, with a specificity of 0.732, a sensitivity of 0.788, and an optimal cutoff value of 15.5%. The AUC of F/T PSA ratio in different age groups (50-59 years, 60-69 years, 70-79 years, and ≥80 years) was 0.767, 0.806, 0.815, and 0.833, respectively, and the best sensitivity (0.857) and specificity (0.802) were observed in patients over 80 years. The T-PSA trend was in accordance with the Gleason score, tumor node metastasis (TNM) stage, and American Joint Committee on Cancer prognosis group. Therefore, the F/T PSA ratio can facilitate the differential diagnosis of PCa and BPD in the broad T-PSA "gray zone". Serum T-PSA can be a Gleason score and prognostic indicator.

Effect of vascular infiltration on the prognosis of patients after radical resection in early gastric cancer / 中华普通外科杂志

Objective:To evaluate the effect of vascular infiltration on the prognosis of patients with early gastric cancer.Methods:A retrospective study was performed on 625 pathologically confirmed early gastric cancer patients at the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital from Jan 2005 to Jan 2014. χ 2 test was used to analyze the relationship between vascular invasion and clinicopathological characteristics; COX proportional hazards model was used to analyze the effect of vascular invasion on the prognosis of patients with early gastric cancer; Kaplan-Meier method was used for survival analysis. Results:There were 625 patients, including 240 (38.4%) in T1a stage and 385(61.6%) in T1b stage. 59 patients (9.4%) had vascular infiltration. Vascular invasion was related to age (χ 2=12.143, P<0.001), depth of tumor invasion (χ 2=27.538, P<0.001) and lymph node metastasis (χ 2=86.846, P<0.001). Multivariate analysis showed that age ( HR=4.370, P<0.001), positive lymph node metastasis ( HR=2.500, P<0.001) and vascular invasion ( HR=2.356, P=0.007) are independent factors affecting the prognosis. The overall 5-year survival rate for the entire group was 84.6%, that without vascular infiltration was 86.0%, significantly higher than 71.2% of those with vascular infiltration ( P=0.001). Conclusion:Age, tumor invasion depth and lymph node metastasis are risk factors for vascular invasion which in early gastric cancer predicts poor prognosis.