Bone metastasis is a common complication in patients with malignant carcinoma. This process involves interactions between metastatic cancer cells and bone microenvironment. The two common pathological types are osteolytic and osteoblastic metastasis. Damage to the bone is closely associated with tumor growth.

Insulin-like growth factor-Ⅰ can promote the breast cancer formation, development and metastasis. According to the characteristic of insulin-like growth factor pathway, the inhibition of insulin-like growth factor pathway signaling can inhibit the growth and metastasis of breast cancer, which is of great significance for breast cancer prevention and treatment.

One hepatitis C virus(HCV) cDNA fragment, 534bp in length and designated as Q534, was obtained by means of PCR amplification with self-designed oligonucleotide primers. Q534 was doned into Hinc II site of pUC18 and the- recombinant plasmid pQ534 was then selected from the bacterial transformants. The sequence data indicated the Q534 was a cDNA fragment of HCV core gene, and located in HCV genome from positions 320 to 853 in correspondence with Chiron's prototype sequence. The homologies between Q534 and the prototype at the levels of nucleotides and amino adds were 90.9% and 97.6%, respectively. The homologies of Q534 with Japanese HCV-J and HCV-BK strains were 96.8% and 97.0% at the nucleotide level, and 98.2% and 98.8% at the amino add level. Compared with the corresponding sequences of other HCV isolates, this Chinese HCV isolate we obtained in the present study belongs to HCV group II .

Hepatitis C virus (HCV) is a major causative agent for sporadic and post-transfusion hepatitis, which frequently progresses into chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. In order to clarify the genomic variations and the structural characteristics of Chinese HCV isolate, we extracted HCV genomic RNA from plasma specimens of Chinese hepatitis C (HC) patients, reverse-transcribed to HCV cDNA with random primers and constructed successfully an HCV cDNA R gt11 library of Chinese type. Two positive clones (Q349 and Q653) were selected by immunoscreening from the library and subcloned into plasmid vector pUC18. Sequence analyses indicated that Q349 was derived from core region (positions 554-902) of HCV genome while Q653 was from NS3 region (positions 4175-4827) corresponding with the prototype HCV nucleotide sequence. The homologies of Q349 and Q653 with the equivalent sequences of HCV prototype were 86.8% and 80.2% at the nucleotide level, and 97.3% and 93.1% at the amino acid level, respectively. It was found that Chinese HCV clones had higher homologies with Japanese HCV isolates, and should belong to HCV group II. Specificity test proved that the encoded peptides of the 2 Chinese HCV cDNA clones reacted specifically with sera from HC patients and had no reaction with sera from healthy individuals. More importantly, clone Q653 showed higher positive reaction rates with Chinese HC sera (95.8%) than those with Japanese ones (85.7%), which strongly suggests that the sequences from Chinese HCV genome (especially from NS regions) would be more suitable for primer designing or peptide synthesis for the use in the detection of HCV infection among Chinese people.

Aim Vascular endothelial cell growth inhibitor(VEGI) is a recently discovered novel member of the TNF superfamily,which is expressed predominantly in endothelial cells.As an endothelial cell-specific negative regulator of angiogenesis,the relationship between structure and function of VEGI is not understood at present.Methods In order to explore the functional key amino acids of VEGI,four mutants of VEGI(E45→R,G47→A,Y111→F,Y111→T) were construced by site-directed mutagenesis,and recombinant proteins were generated from E.coli.Four mutant proteins behaved similar to the wild type VEGI in various physico-chemical assays.The proliferation of HUVEC and chick choriallantic membrane assay were performed to study the activity of four mutants.Results The mutant E45→R significantly decreased the biological activity,and the mutant G47→A caused a slight drop on activity,but the mutants Y111→F,Y111→T almost completely abolished biological activity.Conclusion It suggests that Y111 is an important residue in biological activity,which may play a direct role in receptor recognition.Moreover,the tyrosine ring and hydroxy group of the amino acid are important determinant of biological activity.Additionally,E45 also plays an important role in biological activity of VEGI.

Penetration enhancers are substances to improve the rate or amount of transdermal permeation which is an important factor in transdermal drug delivery systems (TDDS). Recent researches have found that some of the new penetration enhancers have a higher penetration-effect, little irritation, fewer adverse reactions, and stable properties. In this article, domestic and foreign research reports on penetration enhancers have been collected and summarized. The research progress of penetration enhancers were reviewed, with a purpose to provide a reference for reasonable selection of penetration enhancers.

Objective To explore whether stromal cell-derived factor 1 (SDF-1) can promote the clearance of β-amyloid deposition in the brain of APP/PS1 mice and the possible underlying mechanism.Methods Twelve 28-week-old APP/PS1 mice were divided into two groups:a treatment group and a control group.Animals were given the intracerebroventricular injection weekly with PBS or mouse recombinant SDF-1 α for eight weeks.Microglia and Aβ in cerebral cortex and hippocampal region of APP/PS1 mice were detected by immunofluorescence.Results After 8-week treatment,both the relative number and the relative area of Aβ deposits in the mice of treatment group were less than those in the control group.The relative number of plaque associated microglia increased to a significantly greater extent in the cortex and hippocampus in treatment group than those in the control group.Conclusion Injecting SDF-1α significantly reduced amyloid burden in APP/PS1 mice.This effect might associated with the improvement of the chemotoxis of microglia,which promote the phagocytosis of Aβ by microglia.

Objective To analyze quantitatively the safety and efficacy of statin therapy in acute phrase for acute ischemic stroke with the method of meta-analysis.Methods We performed a systematic literature search including the Cochrane Library,MEDLINE and EMBASE for published trials about statin therapy and the outcomes of acute ischemic stroke.Then we performed a meta-analysis with included studies to investigate the association between statin therapy and clinical outcome and mortality.All of the data were pooled and meta-analyzed by Cochrane Collaboration RevMan 5.3 meta-analysis software.Statistical heterogeneity between studies was evaluated by the chi-square and I-square tests.Forest plots were used to summarize study data and Egger tests were used to assess publication bias.Results A total of 27 studies including 52 034 patients,comprising 19 212 statin users and 32 822 non-statin users met the inclusion criteria,4 studies were randomized controlled trials (RCTs),and 23 were observational trials (OTs).Both pre-or post-stroke statin use was associated with reduced mortality.Statin use is associated with favorable functional outcome at hospital discharge and on the ninetieth day regardless of initiation time for pre-stroke group and post-stroke group.The results from observational trials were consistent with randomized controlled trials.There was no evidence of publication bias for all comparisons by Egger tests.Conclusions Statin therapy before or after AIS is safe and effective.

Aim To screen out the antigenic sequences from HCV core protein random peptide libraries displayed on phage and to explore a new way to screen the viral antigens. Methods The anti-HCV core antibody-positive serum was used to screen antigenic peptides from the HCV core protein random peptide libraries displayed on phage for 4 rounds. Detection of numbers of positive clones, positive rate of insertion of HCV random DNA and positive rate of hybridization with HCV core probes were used to evaluate the screening effects. The DNA sequences of 7 selected clones with positive hybridization were determined and analysed. Results Six out of 7 sequences are HCV core protein sequences, in which 5 were perfectly displayed,and one was possibly displayed. These sequences included several major HCV core antigenic epitopes. The remaining one was E.coli nrfa gene. Conclusion The phage display technique can be applied to study the viral antigenic peptides with the advantages of simple, accuracy and rapidity.

Objectives:To assess bowel function and quality of life in patients with ulcerative colitis (UC)after ileal pouch anal anastomosis (IPAA).Methods:Clinical data of 37 UC patients after IPAA between 2014 and 2017 were retrospectively analyzed at Sir Run Run Shaw Hospital School of Medicine Zhejiang University. The IBDQ and Bowel Function questionnaire were used for analyzing correlation between clinical variables and quality of life or bowel function.Results:Laparoscopic operation was performed in 12 cases at stage 2 and 25 cases at stage 3. Postoperative defecation of stage 3 patients were better than that of stage 2 ( t=6.72, P<0.05). The number of daily defecation in age >45-year-old group was more than that in <45-year-old ( t=3.49, P<0.05), and the rate of evening stool seepage in the older group was higher than in the younger group( t=5.28, P<0.05). The total score of intestinal symptoms of IBDQ in patients of pouchitis was lower than that without pouchitis ( r=0.330, P<0.05). The total score in age >45 in terms of systemic symptoms ( r=0.349, P<0.05) and emotional function ( r=0.379, P<0.05) was higher than age <45. Conclusions:Outcomes of UC patients after IPAA are satisfactory, bowel function and quality of life is related with age, and stage of IPAA affect postoperative defecation.