A new series of 3-phenyl-3-pyrrolylpentane derivatives are synthesized through modifying the structure of lead compound LG19055,a nonsecosteroidal vitamin D receptor(VDR)agonist.The VDR-agonistic ability of target compounds was measured indirectly by evaluating the differentiation ability of HL-60 cell.The results showed that compounds 13a,13c,13d,13h,13i,13j have excellent VDR-agonistic ability(EC50 <50 μmol /L), especially for compound 13j (EC50 =0.10 μmol /L),which was more potential than that of lead compound LG190155.Their proliferation inhibitory activities in vitro were evaluated by MTT assay in MCF-7,PC-3,Caco-2, HepG2 and L02 cell lines.Compound 13a exhibited significant inhibitory effects on HepG2 cell line(IC50 =0.11μmol /L).Moreover,the inhibitory effect of compound 13a on non-tumor liver L02 cell line was relatively weak (IC50 =15.24 μmol /L ),suggesting that compound 13a has selective inhibitory effects on liver cancer cells.Additionally,HL-60 cell differentiation-inducing activity and the inhibitory effect of cancer cells were posi-tively related.

Objective To investigate the effect of propofol on the function of gap junction (GJ) in HeLa cells transfected with Cx32/Cx26 plasmid. Methods Cervical cancer HeLa cells transfected with Cx32/Cx26 was given as present by professor Andrew L. Harris from New Jersey Dental Medical School, department of pharmacology and physiology. The transfected cells were selected by G-418. The effective GJ channels were identified by "Parachute Assay". The cells were randomly divided into 6 groups: Ⅰ control group (group C); Ⅱ fat emulsion group was exposed to fat emulsion 10 μg/ml (group E); Ⅲ 18-α-GA group was exposed 18-α-GA (gap junction blocker) 1.0 μg/ml (18-α-GA); Ⅳ, Ⅴ, Ⅵ propofol groups were exposed to propofol 1.3, 2.2 and 3.2μg/ml respectively (group P1, P2, P3). The transfected HeLa cells were incubated at 37 ℃ for 4 h. Gap junction function was assessed using fluorescent indicators Calcine-AM which emits green fluorescence and CM-Dil which emits red fluorescence. The small molecular Calcine-AM can pass through gap junction and enters HeLa cells while the large molecular CM-Dil cannot pass through gap junction and stays in the loading cells. Fluorescent indicator transmissibility and inhibition rate were calculated. Results The fluorescent indicator transmissibility was significantly lower and inhibition rate higher in group 18-α-GA, P1, P2 and P3 than in control group. There was nosignificant difference in the fluorescent indicator transmissibility and inhibition rate between group C and E. The inhibition of GJ function by propofol was dose-dependent. Conclusion Propofol can inhibit the function of GJ in HeLa cells transfected by Cx32/Cx26 in a dose-dependent manner.

Aim To study the effect of emodin in Po-lygonum multiflorum on the expression of CYP450 isoenzymes in L02 hepatocytes and explore its mecha-nism of cytotoxicity. Methods L02 cells were treated with different concentrations of emodin. Cell viability was examined by MTS assay kit, and cell membrane injury was examined by detecting the release rate of lactate dehydrogenase( LDH) . The expression of cyto-chrome P450 mRNA was detected by real time PCR. Results The result of MTS assay showed that L02 cells viability was significantly reduced following expo-sure to emodin in a concentration and time dependent manner. The LDH release rate of L02 cells significant-ly increased after exposure to emodin for 48 h com-pared with the control group. On the mRNA level, compared with the control group,emodin had inductive effects on mRNA of each CYP450 enzyme, while had significant inductive effects on mRNA of CYP1 A1 and CYP1 B1 in a concentration and time dependent man-ner. Conclusion Emodin in Polygonum multiflorum may generate significant liver injury in L02 cells and has inductive effects on CYP450 enzyme activity.

Purpose: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. Results: One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). Conclusion The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.