Objective To study the rational daily administration times of Yinchenhao Decoction (YCHD) when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.MethodsRats were modeled by 4％ 1-naphthylisothiocyanate (75 mg/kg) for 48 h,then YCHD was drenched with doses of 0.324 g/kg (extract,calculated with the clinical dosage) once,0.162 g/kg twice,and 0.108 g/kg thrice a day,respectively.The total bile and the flow rate of bile were observed after the first administration; Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes (ALT and AST) and bilimbins (TBIL and DBIL),and determine the concentration of 6,7-dimethoxycoumarin (DME) in the plasma using UPLC at the same time,then we obtained the time-effect and time-dose curves.The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships.ResultsWithin 10 h the total bile of rats which were administered once daily (G1) was I.65 and 1.33 times higher than that of twice and thrice (G2 and G3) a day,respectively,and the four biochemical indexes (TBIL,ALT,DBIL,and AST) of Gl decreased faster than those of G2 and G3 (P ＜ 0.05).On the other hand,the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time,and its Cmax and AUC0→t were higher than those of G2 and G3,which might be the main reason why its effect was the most significant.ConclusionIt is more appropriate to administrate once daily when YCHD is used to treat jaundice.

To compare the microcalorimetric fingerprint profiles of Lonicerae japonicae Flos (Lj.F) and Lonicerae Flos (L.F), microcalormietry was applied to find the heat change regularity of Bacillus shigae (B. shigae) metabolism affected by Lj.F and L.F (we choose Lonicera macranthoides Hand.-Mazz in this paper) with different concentrations. The thermogenic curves and thermodynamics parameters were investigated as evaluation index, and then the date of experiment was studied by similarity analysis. All the results indicated that the Lj.F and Lonicera macranthoides Hand.-Mazz (L.m.H-M) significantly impacted the microbial growth and had good similarity in its inhibitory activities. The combination approach of chemical analysis with bioassay was developed and employed to ensure the safety and efficacy of Chinese herbal medicines.

OBJECTIVETo study the rational daily administration times of rhubarb when it is used to treat experimental jaundice in rats, at the same time, validate the accuracy and feasibility of the method which was previously established to research the rational daily administration times of rhubarb (PD-PK method), and consummate it.

METHODAfter the rats were modeled by 4% ANIT (75 mg x kg(-1)) for two days, rhubarb extraction was drenched 3.6 g x kg(-1) once a day, 1.8 g x kg(-1) twice a day and 1.2 g x kg(-1) three times a day, respectively. Then the total bile and the flow rate of bile were observed. Blood was collected from the veins behind the eye sockets after different intervals and was used to investigate the biochemical indexes of the blood serum, such as TBIL, ALT, ALP, AST and GGT, and to determine the concentration of rheic acid in the blood plasma, then the time-effect curve and time-dose curve were obtained. The rational daily administration times of rhubarb was determined when it was used to treat experimental jaundice based on the comprehend analysis of time-effect and time-concentration relationships.

RESULTCompared with the groups which were administered once a day and three times a day, the total bile within 8 h of the rats which were administered twice a day was 1.56 and 1.7 times higher, respectively, while the TBIL was 23%, 22%, and ALT was 86%, 65% of the other two, ALP was 50%, 71% of the other two, respectively. With administrated twice a day, the blood concentration of rheic acid could maintain a high level for a longer time, which maybe the main reason for its effect.

CONCLUSIONThe method based on pharmacodynamics and pharmacokinetics is scientific and feasible to study the rational daily administration times of traditional Chinese medicine. Rhubarb is better to administrate two times a day to treat jaundice.

Alkaline Phosphatase ; blood ; Animals ; Bile ; drug effects ; Female ; Jaundice ; drug therapy ; physiopathology ; Male ; Plant Extracts ; pharmacokinetics ; therapeutic use ; Rats ; Rats, Wistar ; Rheum

Objective To discuss the utility of contrast-enhanced ultrasonography (CEUS) in the assessment of treatment efficacy of radiofrequency ablation (RFA) in patients with renal tumors.Methods Forty-seven patients (40 renal cell carcinomas and 7 angiomyolipomas of kidney) with 49 renal tumors were treated with RFA. Tumors were ablated by laparoscopy-assisted (n= 30) and open surgical (n= 17) RFA. The CEUS and contrast-enhanced CT were performed 1 week after treatment to assess the necrotic area. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. Results Forty-seven (95. 9%) of 49 tumors were successfully ablated. The mean length of the major axis at the maximal necrotic area was 4. 6 cm. Compared with the lesions before RFA, the necrotic areas were bigger in 45 patients, identical in 3 patients, and smaller in 1 patient. Six lesions showed a residual enhancement at the portion adjacent to the normal renal parenchyma on follow-up CEUS, while 2 were confirmed by CT scans. The sensitivity and specificity of CEUS for detection of residual tumors were 100. 0% and 91.8%, respectively. All patients survived in the follow-up period ranging from 4 to 21 months. Conclusion CEUS combined with CT could be useful for evaluating treatment efficacy of RFA for renal tumors.

Objective To investigate the expression of circular-RNA DDX5(circ-DDX5)in breast cancer tissues and its relationship with the clinical stage of breast cancer patients,and to analyze the regulatory mechanism of circ-DDX5 on the proliferation and invasion of human breast cancer cell line.Methods The expression level of circ-DDX5 in breast cancer tissues and its correlation with the clinical stage of breast cancer patients were analyzed by TCGA database.Bioinformatics analysis and dual-luciferase reporter gene experiments verified the targeting rela-tionship between circ-DDX5 and miR-3940.The correlation between circ-DDX5 and miR-3940 expression in breast cancer tissues was analyzed by TCGA database.The expression level of circ-DDX5 in breast cancer SK-BR-3,MDA-MB-231,BT-549,MCF-7,and HCC-1937 cells was detected by RT-qPCR.The circ-DDX5 over-expression plasmid and negative control plasmid were transfected into MDA-MB-231 cells,which were named circ-DDX5 group and NC group,respectively.The proliferation and invasion of MDA-MB-231 cells in the circ-DDX5 group and the NC group were detected by colony formation assay and Transwell assay.The expressions of proliferation pheno-type protein and invasion phenotype protein of MDA-MB-231 cells were detected by Western blot.The expression level of miR-3940 in MDA-MB-231 cells of circ-DDX5 group and NC group was detected by RT-qPCR.Results The expression of circ-DDX5 in breast cancer tissues was lower than that in adjacent tissues(P＜0.01)and the ex-pression level of circ-DDX5 was negatively correlated with the clinical stage of breast cancer patients(P＜0.01).There was a targeting relationship between circ-DDX5 and miR-3940(P＜0.01).The expression of circ-DDX5 and miR-3940 in breast cancer tissue was negatively correlated(P＜0.01).The expression of circ-DDX5 in human breast cancer cell lines was lower than that in immortalized breast epithelial cells MCF-10A(P＜0.05 or P＜0.01).Compared with the NC group,the over-expression of circ-DDX5 could significantly inhibit the proliferation and in-vasion of MDA-MB-231 cells(P＜0.01),as well as the proliferation phenotype proteins(cyclin C,CDK3)and in-vasion phenotype proteins(Snail,vimentin)expression(P＜0.01)and miR-3940 expression(P＜0.01).Conclu-sions The expression of circ-DDX5 in breast cancer tissues and cells is low.circ-DDX5 inhibits the proliferation and invasion of breast cancer MDA-MB-231 cells by targeting the expression of miR-3940.

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.