Approximately 70％ advanced breast cancer will develop bone metastases.Bone metastases can cause a series of complications such as skeletal-related events,seriously affecting the quality of life of the patients.Therefore,it is very important to choose the reasonable and effective treatments.Bisphosphonates are the standard treatments of bone metastatic breast cancer,denosumab may also be a reasonable alternative to bisphosphonates in the near future,while chemotherapy,endocrinotherapy and targeted therapy are the basic treatments of advanced breast cancer,combined use of various treatments will get the best efficacy.

Objective To quantify the expression levels of calpain 1 and caspase-3 in lichen planus (LP) lesions and their relationship with the apoptosis in keratinocytes.Methods Biopsy samples were obtained from the lesions of 20 patients with LP and normal skin of 10 healthy controls,and embedded in paraffin.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used to evaluate the apoptosis in keratinocytes,and immunohistochemical staining to detect the expressions of calpain 1 and caspase-3,in these tissue specimens.Data were processed by SPSS 13.0 software.Comparison analysis was carried out by t test for apoptosis index,and by rank sum test for the expressions of calpain 1 and caspase-3.Spearman correlation analysis was conducted to evaluate the relationship between these parameters.Results The apoptosis index of keratinocytes was higher in LP lesions than in the normal skin (67.59 ± 13.50 vs.28.26 ± 7.56,t =8.52,P ＜ 0.01).Significantly increased expressions of calpain 1 and caspase-3 were observed in the epidermis of LP lesions compared with the normal skin (T =78.00 and 77.00,respectively,both P ＜ 0.01).The expressions of both calpain 1 and caspase-3 were positively correlated with apoptosis index of keratinocytes (r =0.71 and 0.74,respectively,both P ＜ 0.01).Conclusions The expressions of calpain 1 and caspase-3 are upregulated in LP lesions,which may be closely associated with the accelerated apoptosis in keratinocytes.

Objective To investigate the effects of DRD1 rs265981,rs4532,rs686 and rs265976 polymorphisms on response to clozapine in resistant schizophrenic patients.Methods DRD1 genotype was determined by SNaPshot SNP technique for 154 patients with resistant schizophrenia.Clinical symptoms were evaluated by Positive and Negative Syndrome Scale (PANSS),and the responder was defined as a reduction of 50％ on PANSS score from baseline after the patients were administered orally clozapine for 8 weeks.Results The frequencies of rs265981 genotypes,alleles and rs265976 genotypes had significant differences between clozapine responder group (88 cases) and nonresponder group(66 cases) in total clinical efficacy ( x2 =10.215,P =0.004 ; x2 =4.082,P =0.041 ; x2 =14.083,P =0.007 ).The frequencies of rs265976 genotypes had significant differences between clozapine response (58 cases) and nonresponse (96 cases) to negative symptom ( x2 =9.805,P =0.046).Conclusion The polymorphisms of DRD1 gene rs265981 and rs265976 may relate with clinical response to clozapine in resistant schizophrenias.rs265981 T/T,allele T and rs265976 genotype A/A are likely to be predictive factors to the improvement of total clozapine therapeutic effects.rs265976 genotype A/A are likely to be predictive factors of negative symptom with treatment of clozapine.

Objective To explore the cytotoxicity of the cytotoxic T lymphocyte (CTL) induced by SW480 sonicate sensitized dendritic cells (DC) on the colon cancer cell line SW480. Methods PBMC were separated from the HLA-A*0201 donor and DC were cultured with rhGM-CSF, rhIL-4 and rhTNF-α. The same donor's primary CTL were stimulated by DC loaded with SW480 sonicate. The cytotoxicity of CTL on SW480 (HLA-A*0201 positive) and K562 (HLA-A*0201 negative) was determined by the MTT method. Results The cytotoxicity of the CTL on SW480 was stronger than that on K562 (P ＜0.05). Conclusion The DC vaccine can stimulate specific CTL which can trigger cytotoxic activity on the target cells and this cytotoxicity is related to MHC restriction.

Objective:To analyze the immune function regulation and clinical effect of dust mite drops desensitization treatment on children with allergic rhinitis.Methods:80 patients with allergic rhinitis and adenoid hypertrophy treated in our department from January 2012 to June 2014 were selected and randomly divided into experimental group and control group.Control group was treated with ebastine and levocabastine treatment, the experimental group was treated with sublingual containing Dermatophagoides Farinae Drops on the basis of control group.The level of IL-2,IL-6,house dust mite specific IgE (sIgE),dust mite IgE (T-IgE),house dust mite specific IgG4 ( sIgE in) ,blood addicted eosinophile cells ( EOS) ,and induced sputum EOS level were compared between the two groups before treatment and after 2 years treatment.Results:The level of IL-2 in the two groups was significantly higher than that before treatment,the level of IL-6 was significantly lower than that before treatment ( P<0.05 ) .After treatment, the level of IL-2 in the experimental group was significantly higher than that in the control group, the level of IL-6 was significantly lower than that in the control group( P<0.05 ).After treatment, the level of sIgE, T-IgE, blood EOS and induced sputum EOS in the two groups were significantly lower than before treatment,the level of sIgG4 were significantly higher than those before treatment (P<0.05).After the treatment,the level of sIgE, T-IgE, blood EOS and induced sputum EOS in experimental group were significantly lower than control group,and the level of sIgG4 was significantly higher than that in control group ( P<0.05).After treatment,the asthma symptom scores and nasal symptom scores of the two groups were significantly lower than before treatment (P<0.05),and those index of experimental group after treatment were significantly lower than control group ( P<0.05 ).Conclusion: Combine the basis of conventional therapy plus with Dermatophagoides Farinae Drops in the treatment of allergic rhinitis and adenoid hypertrophy children can effectively regulate the immune function of the patients,has good clinical efficacy.

BACKGROUND:Studies have shown that the number of osteoblasts is often decreased after osteoporosis, and osteoblast replacement therapy becomes a new target for the treatment of osteoporosis. OBJECTIVE:To observe the osteogenic differentiation of human bone marrow mesenchymal stem cels cultured in dexamethasone, vitamin C and beta-glycerophosphate. METHODS:Mesenchymal stem cels were isolated and purified from adult bone marrow using human lymphocyte separation medium. The expression of cel surface markers was detected by flow cytometry. Cel ultrastructure was observed by transmission electron microscope. Then, the bone marrow mesenchymal stem cels were cultured in osteogenic induction medium containing dexamethasone, vitamin C andβ-glycerophosphate, and RT-PCR was used to detect the bone morphogenetic protein-2 mRNA expression after osteogenic induction. RESULTS AND CONCLUSION:A large number of adherent cels were visible as fibrous growth at 2 weeks after culture and strongly expressed CD44, CD29, but did not express CD34, CD45. These cels could be induced to differentiate into osteoblasts, and express bone morphogenetic protein-2 mRNA. Alizarin red staining and alkaline phosphatase staining were positive for the cels. These findings suggest that human bone marrow mesenchymal stem cels cultured in dexamethasone, vitamin C and beta-glycerophosphate can differentiate into osteoblasts, and has a potential for the treatment of osteoporosis.

Objective To provide theoretical guidance for further research on the role of miR-1 99a-3p in formation and development of bladder cancer.Methods Mature sequence of miR-1 99a-3p was analyzed;target genes and transcription factors of miRNA-1 99a-3p were predicted,and the target genes were analyzed for gene ontology (GO)enrichment and Kyoto Encyclopedia of Genes and Genome (KEGG)pathway.Then TF-miRNA-mRNA network diagram was constructed.Results Sequences of miR-1 99a-3p were highly conserved in various species.In GO analysis,the target genes of miR-1 99a-3p were enriched in many biological processes,such as regulation of cellular process,regulation of macromolecule metabolic process,and regulation of biological process (P <0.01 ).In KEGG pathway,the target genes were mainly located in bacterial invasion pathway of epithelial cells,ECM-receptor interaction pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,small cell lung cancer pathway,and proteoglycans pathway in the cancer (P <0.05).According to the TF-miRNA-mRNA network diagram,the important genes that might be regulated by miR-1 99a-3p were MYC,SP1,mTOR,NFκB,and NFκB1.Conclusion miR-1 99a-3p may directly target mTOR and participate in the formation and development of bladder cancer through regulating PI3K-Akt-mTOR signaling pathway.

Objective:To study the curative efficacy of budesonide combined with huaiqihuang granules in the treatment of children with asthma and its effects on the serum leukotriene D4(LTD4),nerve growth factor (NGF),tissue inhibitor of metalloproteinase-1 (TIMP-1) levels.Methods:90 cases of children with asthma who were treated from March 2014 to March 2015 in our hospital were selected and divided into the observation group (n=45) and the control group (n=45) according to the random number table.Both groups of children were given bronchial antispasmodic agent,oxygen,antibiotics,glucocorticoid and other conventional treatment after admission,the control group was given budesonide atomization inhalation treatment on the basis of conventional treatment,0.5 mg budesonide were add in 3ml saline for continuous inhalation,twice a day,while the observation group was treated with Huaiqihuang Granules on the basis of the control group,twice a day.After 12 weeks of treatment,the curative effect,disappearance time of wheezing,cough relief,pulmonary rales,wheezing and other symptoms,forced vital capacity (FVC),serum LTD4,NGF,TIMP-1 levels,CD3+,CD4+,CD8+ of both groups were compared.Results:After treatment,the total effective rate of observation group was significantly higher than that of the control group [93.33％(42/45) vs 77.77％(35/45)](P＜0.05);disappearance time of breath,cough,moist rales and wheezes were significantly shorter than those of the control group[(4.32± 1.03)d vs (6.08± 1.24)d,(5.60± 1.12)d vs (7.21± 1.30)d,(3.19± 0.98)d vs (4.98± 1.02)d,(3.25± 1.03)d vs (5.89± 1.35)d](P＜0.05);the FEV1,FEV1/FVC were significantly higher than those of the control group [(92.63± 10.01)L/s vs (78.36± 9.19)L/s,(95.37± 11.72)％ vs (80.19± 10.23)％](P＜0.05);the serum LTD4,NGF,TIMP-1 levels were significantly lower than those of the control group [(7.24± 0.86)ng/mL vs (12.68± 1.01vng/mL,(68.18± 9.01)pg/mL vs (80.78± 10.24)pg/mL,(34.16 ± 5.06)ng/mL vs (49.76 ± 5.47)ng/mL] (P ＜0.05);the CD3+,CD4+ were significantly higher than those of the control group [(66.15± 7.20)％ vs (62.03± 6.85)％,(45.13± 7.90)％ vs (37.42± 7.06)％],CD8+ was significantly lower than that of the control group[(34.16± 5.06)％ vs (49.76± 5.47)％] (P＜0.05).Conclusion:Budesonide combined with Huaiqihuang granules was effective for children with asthma,which could enhance the immune function,improve the lung function,reduce the serum levels of LTD4,NGF,TIMP-1.

Objective To explore the role of miRNA-148a in bladder tumorous development and progression.Methods Ex-pression of miRNA-148a was assessed in 35 bladder carcinoma tissues and 16 non-carcinoma tissues by fluorescence quanti-tative real time PCR,and correlation with clinical features was evaluated.Target genes and transcription factors of miRNA-148a were predicted using bioinformatic analysis,then TF-miRNA-148a-target genes network diagram was built and the tar-get genes was analyzed of gene ontology enrichment and KEGG pathway.Results Expression of miRNA-148a was lower in bladder carcinoma tissues than in non-carcinoma tissues(0.000 8±0.000 2 vs 0.002 1±0.000 5)(t=2.46,P <0.05),but its expression was no statistical significance in different groups of gender,age,pathological classification,clinical stage, lymph node metastasis (P >0.05).268 target genes of miRNA-148a were predicted by three softwares at the same time,60 transcription factors were predicted and the binding sites with combination scroes above 80 was 657.The target genes of miRNA-148a was enriched in many biological processes,such as neuron differentiation,generation of neurons,neuron projec-tion development,cytoplasmic mRNA processing body,cytoplasm(P <0.001).They also participated in p53 signaling path-way,proteoglycans in cancer-homo sapiens,pathways in cancer,prostate cancer,protein processing in endoplasmic reticulum, focal adhesion and so on(P <0.05).According to TF-miRNA-148a-target genes network diagram,miRNA-148a was regula-ted by SP1,ESR1,AP1,MYC and BRCA1,genes of IGF1,P27kip1 ,NCOA1,PTEN,SERPINE1 might be regulated by miR-NA-148a.Conclusion miRNA-148a which was significantly down-regulation in bladder carcinoma tissues may be participate in bladder tumorous development and progression,bioinformatics analysis provides some ideas for further research.

Objective To investigate the influence of Herba Epimedium, a kidney-strengthening Chinese herb, on the regenerate ossification of nano-hydroxyapatite/collagen/ polylactic acid (nHAC/PLA) in the repair of rabbit mandibular defect. Methods Sixteen rabbit models with 10 mm × 8 mm subperiosteal mandibular defect were established. The rabbits were randomly divided into 2 groups, namely Herba Epimedium group and control group. In both groups, the left mandibular defect region (short for left side) was not filled with any material, while the right mandibular defect region ( short for right side) was filled with nHAC/PLA. On week 2, 4, 8, 12 after modeling, rabbits in each group were killed, and then the macro-view, imageology and histology of the bilateral mandibles were observed. The data of the regenerate bone areas were calculated and analyzed with analysis of variance (ANOVA) . Results The imageological results showed bone mineral density in the right side of Herba Epimedium group and the control group, and in the left side of Herba Epimedium group were higher than those in the left side of the control group on week 2, 4, 8, 12 after modeling. The histological results showed that the regenerate ossification in the right side of Herba Epimedium group and the control group was superior to that in the left side of the corresponding groups, with more regenerative bone and vessels. In the right side of Herba Epimedium group and the control group, amount of bone-like tissues were grown into nHAC/PLA, and the maturity degree of bone tissue was increased with the prolongation of time. And the changes were more obvious in the right side of Herba Epimedium group, showing as the remaining of nHAC/PLA having been surrounded and replaced by regenerative bone tissue. Regenerative bone area was increased in both sides of Herba Epimedium group, which differed from the same side of the control group (P<0.05) . The differences of the regenerative bone area were also significant between the left side and right side of the same group (P<0.05) . Conclusion Herba Epimedium can effectively accelerate the repair of mandibular defect, and nHAC/PLA is of good biocompatibility, osteoinduction and bone conduction, and can be expected for bone defect repairing in clinic.