Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,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.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China

BACKGROUND Through analyzing the data from a single institution in Northeast China,this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer(GC).AIM To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China,which is a highprevalence area of GC.METHODS The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital.The study mainly analyzed the data in three periods,2000 to 2004(Phase 1),2005 to 2009(Phase 2),and 2010 to 2014(Phase 3).RESULTS Over time,the postoperative survival rate significantly increased from 2000 to 2014.In the past 15 years,compared with Phases 1 and 2,the tumor size was smaller in Phase 3(P<0.001),but the proportion of high-medium differentiated tumors increased(P<0.001).The proportion of early GC gradually increased from 3.9%to 14.4%(P<0.001).A surprising improvement was observed in the mean number of retrieved lymph nodes,ranging from 11.4 to 27.5(P<0.001).The overall 5-year survival rate increased from 24%in Phase 1 to 43.8%in Phase 3.Through multivariate analysis,it was found that age,tumor size,histologic type,tumor-node-metastasis stage,depth of invasion,lymph node metastasis,surgical approach,local infiltration,radical extent,number of retrieved lymph nodes,and age group were independent risk factors that influenced the prognosis of patients with GC.CONCLUSION The clinical features of GC in Northeast China changed during the observation period.The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

Prognostic significance of Borrmann type combined with vessel invasion status in advanced gastric cancer

BACKGROUND Borrmann classification(types I-IV)for the detection of advanced gastric cancer has been accepted worldwide,and lymphatic and/or blood vessel invasion(LBVI)status is related to the poor prognosis after gastric cancer.AIM To evaluate the significance of Borrmann type combined with LBVI status in predicting the prognosis of advanced gastric cancer.METHODS We retrospectively studied the clinicopathological characteristics and long-term survival data of 2604 patients who were diagnosed with advanced gastric adenocarcinoma at Harbin Medical University Cancer Hospital from January 2009 to December 2013.Categorical variables were evaluated by the Pearson’sχ^2 test,the Kaplan-Meier method was used to identify differences in cumulative survival rates,and the Cox proportional hazards model was used for multivariate prognostic analysis.RESULTS A total of 2604 patients were included in this study.The presence of LVBI[LBVI(+)]and Borrmann type(P=0.001),tumor location(P<0.001),tumor size(P<0.001),histological type(P<0.001),tumor invasion depth(P<0.001),number of metastatic lymph nodes(P<0.001),and surgical method(P<0.001)were significantly correlated with survival.When analyzing the combination of the Borrmann classification and LBVI status,we found that patients with Borrmann type Ⅲ disease and LBVI(+)had a similar 5-year survival rate to those with Borrmann IV+LBVI(-)(16.4%vs 13.1%,P=0.065)and those with Borrmann IV+LBVI(+)(16.4%vs 11.2%,P=0.112).Subgroup analysis showed that the above results were true for any pT stage and any tumor location.Multivariate Cox regression analysis showed that Borrmann classification(P=0.023),vascular infiltration(P<0.001),tumor size(P=0.012),pT stage(P<0.001),pN stage(P<0.001),and extent of radical surgery(P<0.001)were independent prognostic factors for survival.CONCLUSION Since patients with Borrmann Ⅲ disease and LBVI(+)have the same poor prognosis as those with Borrmann IV disease,more attention should be paid to patients with Borrmann Ⅲ disease and LBVI(+)during diagnosis and treatment,regardless of the pT stage and tumor location,to obtain better survival results.

清热利湿护肝方治疗肥胖型非酒精性脂肪性肝病患者的临床效果

目的探讨清热利湿护肝方治疗肥胖型非酒精性脂肪性肝病患者的临床效果。方法选取2020年11月至2021年3月西安市高陵区中医医院脾胃肺病科收治的102例肥胖型非酒精性脂肪性肝病患者为研究对象,根据随机数字表法将其分为对照组和研究组,各51例。对照组给予常规西药治疗,研究组在对照组基础上给予清热利湿护肝方治疗。比较两组的中医证候积分、临床疗效、肝功能及血清学指标水平。结果治疗后,两组的胁下胀痛或不适、周身困重、纳呆、胸脘痞满、形态肥胖、肢倦乏力评分均降低,且研究组低于对照组,差异具有统计学意义(P<0.05)。研究组的治疗总有效率显著高于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的GGT、AST、ALT、ALP、DBIL、TBIL水平均降低,且研究组低于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的APN水平升高,PAI-1、FGF21、sCD163、Vaspin、TNF-α水平均降低,且研究组优于对照组,差异具有统计学意义(P<0.05)。结论清热利湿护肝方治疗肥胖型非酒精性脂肪性肝病患者的效果显著,可降低中医证候积分,改善肝功能及血清学指标水平。

Financing Model Decision of Inter-basin Water Transfer Projects

Inter-basin Water Transfer Projects require the appropriate financing model to attract large amounts of social investment.Therefore,financing model decision becomes the key of engineering construction.In three aspects,such as the subject,the object and the target of the financing model,Grey Target Model is established in this paper.First,the complex financing mode decision problems of Inter-basin Water Transfer Projects are decomposed by using hierarchical decomposition method.Then Analytical Hierarchy Process(AHP) method is used to calculate the comprehensive weight of evaluation index.Experts' opinions financing model are transformed into the evaluation matrix based on the Dephi method.The Weighted Grey Target Model is used to calculate the approaching degree of financing model and assists financing mode decision.In addition,this paper takes the water diversion project from the Han to the Wei River of Shaanxi Province as a verification example for the model.For other water diversion projects,the evaluation results are also reliable and provide theoretical references for the financing model decision of Inter-basin Water Transfer Projects.

The Development and Comparative Analysis of Engineering Project Management Modes

Engineering project management is the whole process of project construction management activities up to the point of achieving the goals of engineering construction, which adopts the means of planning, organizing,leading, and controlling. In addition, engineering project management modes are the works of project management and the technical guarantee of project success. For the quality and efficient transformation demands of the Chinese construction industry in the process of marketization, internationalization and informatization, based on the connotation and development path of engineering project management modes, the 16 main and new kinds of project management modes both domestically and abroad are divided into trading mode, financing mode and management mode. These have led to comparative analysis and brief commentary. Finally, it will be pointed out that the engineering project management modes move throughout the whole management process, the combined model and the expansion development of financing model. This work will provide reference for project participants to choose the appropriate project management modes and better understand building company transformation.