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Objective To observe the effects of tetrandrine on the proliferation,migration,and invasion of melanoma cell B16,and to explore its effects on epithelial mesenchymal transition(EMT)and potential regulatory mechanisms.Methods(1)The proliferation of B16 cells was detected by CCK-8 assay after 0,2,4,6,8 and 10 μmol·L-1 of tetrandrine intervention for 24 and 48 hours.The colony formation ability of B16 cells was detected by plate clone formation assay after 1,2 and 4 μmol·L-1 of tetrandrine intervention;the migration and invasion ability of B16 cells was detected by cell scratch assay and Transwell invasion assay;the expressions of N-cadherin,Vimentin and E-cadherin related to EMT in B16 cells were detected by Western Blot assay.The mouse melanoma lung metastasis model was replicated by tail vein injection of B16 cells to observe the effects of tetrandrine(50 and 100 mg·kg-1)administered by gavage on the number of metastatic tumor nodules in the lungs of mice.(2)The CTD,SwissTargetPrediction and Similarity Ensemble Approach databases were used to predict the targets of tetrandrine;the GeneCards database was used to search for targets related to melanoma disease;the intersection of these two databases was taken as the potential target of tetrandrine for melanoma treatment.The intersected targets were imported into STRING database to construct protein-protein interaction(PPI)network and screen the core targets;the intersected targets were imported into DAVID database for GO function and KEGG pathway enrichment analysis;and molecular docking between tetrandrine and the core targets was verified by Autodock software.(3)In vivo experimental validation:after intervention of 1,2 and 4 μmol·L-1 tetrandrine,Western Blot method was used to detect the expression of the key pathway AKT/NF-κB/CREB pathway-related proteins;and AKT agonist SC79 was used to validate the replication experiments.Results(1)The IC50 of B16 cells intervened by tetrandrine was 4.273 and 4.085 μmol·L-1 at 24 and 48 hours.Compared with the control group,the colony forming ability,scratch healing rate and invasion rate of cells in the 1,2 and 4 μmol·L-1 tetrandrine group were all significantly reduced(P<0.05,P<0.01,P<0.001);the expressions of cellular Vimentin and N-cadherin protein expressions were significantly down-regulated(P<0.01,P<0.001),and E-cadherin protein expression was significantly up-regulated(P<0.01,P<0.001).Compared with the model control group,the number of melanoma lung metastatic nodules was significantly reduced in the mice in the high-dose group of tetrandrine(P<0.05).(2)A total of 60 potential targets were obtained for the treatment of melanoma with tetrandrine;core targets such as AKT1,TNF,CCND1,RELA,CASP9,CHUK,and CREBBP were further screened,among which AKT1 was the most strongly interacting target;the signaling pathways such as apoptosis,FoxO,TNF,PI3K-AKT,and NF-κB were mainly involved.The molecular docking showed that tetrandrine had strong binding activity with AKT1,TNF,RELA and other core targets.Compared with the control group,protein expressions of p-AKT/AKT,p-NF-κB p65/NF-κ B p65,and p-CREB/CREB were significantly down-regulated in the cells of the tetrandrine 1,2,and 4 μmol·L-1 groups(P<0.05,P<0.01);protein expressions of p-AKT and p-NF-κB p65 were significantly up-regulated in the cells of the SC79 group(P<0.001).Compared with the SC79 group,protein expressions of p-AKT,p-NF-κB p65,and p-CREB were significantly down-regulated in the cells of the 2 μmol·L-1 tetrandrine+ SC79 group(P<0.001).Conclusion Tetrandrine may inhibit the proliferation,migration,invasion and EMT of mouse melanoma by regulating the AKT/NF-κB/CREB pathway,and thus inhibit the lung metastasis of mouse melanoma.
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Objective To explore the potential genetic variants related with late-onset Alzheimer's disease(LOAD),and to broaden the AD genetic susceptibility factor profile.Methods We targetedly sequenced four lipids metabolism related genes including apolipoprotein E(APOE),sortilin-related receptor gene (SORL 1),apolipoprotein C-I (APOC1) and clusterin (CLU),validated these candidate variants in patients with LOAD and mild cognitive impairment (MCI)and the controls with normal cognitive function,and made a bioinformatic analysis.Results The mutation in the allele of CLU rs117389184,a low-frequency single nucleotide polymorphism,would increase the risk of LOAD and MCI[OR (95 % CI):3.56 (1.08-4.84),P =0.026;OR (95 % CI):3.06 (0.98-4.03),P =0.026],suggesting CLU rs117389184 gene variant was associated with cognitive impairment.This variation could affect CLU gene expression by interfering with the binding of transcription factors.Conclusions CLU rs117389184 is a new genetic risk variant for LOAD and MCI.
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Objective To explore the effect of forgiveness intervention on improving the happiness index and self-esteem of the elderly.Methods Totally 103 cases who had been offended and did not relieved were enrolled in this research.Two groups were assigned using digital random method.There were 49 cases in the experimental group and 50 cases in the control group that were counted in final statistics according to the inclusion and exclusion criteria.The experimental group received 8-week forgiveness therapy,control group re-ceived no special intervention.Results The scores of well-being,forgiving self,forgiving others and self-es-teem respectively were 3.06±0.97,3.23±0.62,3.01±0.63 and 2.71±0.35 respectively.Forgiving others was positively related with well-being and self-esteem(r=0.296,0.273,P<0.01),and there was no correlation between forgiving self and well-being(r=0.113,P>0.05). Forgiving others(t=5.309,P<0.01),self-esteem (t=2.732,P=0.008),well-being(t=2.732,P=0.008)in experimental group were improved after the inter-vention,but no difference was found in forgiving self(t=1.413,P=0.165). And there were significant differ-ence in both main effect and interaction effect in forgiving others(Fmain=39.05,Pmain<0.01; Finter=34.96, Pinter<0.01),self-esteem(Fmain=26.41,Pmain<0.01; Finter=35.83,Pinter<0.01),well-being(Fmain=20.96,Pmain<0.01;Finter=18.06,Pinter<0.01)at the pre-test,post-test and 1 month after intervention in experimen-tal group. In the control group,there was no significance in main effect(Fmain=1.98,Pmain=0.152),but the interaction effect was significantly different(Finter=10.98,Pinter<0.01).Conclusion Forgiveness interven-tion can improve forgiveness for elderly people.This intervention method has a positive effect on improving the overall happiness index and self-esteem of elderly people who have been subjected to other offenses,unfair treatment or interpersonal conflicts.
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Objective To investigate the relationship among Machiavellianism,loneliness and coping style in adolescents.Methods 850 junior middle school students were recruited and assessed with Kiddie Machiavellianism Scale,Self-esteem Scale,and Strengths and Difficulties Questionnaire (for students).Mediating effect was analyzed by multiple regression analysis.Results ① The scores of Machiavellianism,loneliness,positive coping and negative coping were (37.35±7.52),(30.21 ± 10.72),(21.07±6.12) and (9.44± 3.84) respectively.② Machiavellianism was positively correlated with negative coping style (r=0.192,P<0.01) and loneliness (r=0.263,P< 0.01),as well as negatively correlated with positive coping style (r=-0.244,P<0.01).③ Positive coping style partially mediated the effect of Machiavellianism on loneliness,and the mediating role accounted for 37.72% for the whole effect.Conclusion The higher the Machiavellianism is,the more serious the loneliness is.Positive coping style partially mediates the relations between Machiavellianism and loneliness.
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Objective To investigate the inhibitory effect of Lycium barbarum polysaccharide ( LBP) on the tumor growth and metastasis in MMTV?PyMT mouse model of breast cancer. Methods The population of MMTV?PyMT trans?genic mice was expanded and identified. 8?week old MMTV?PyMT?positive female mice were randomly divided into LBP group and control group, 8 mice in each group. The mice of LBP group were given LBP treatment (50 mg/kg, i. p. ), and the control group was given normal saline in the same volume, once every 2 days for 4 weeks. The tumor size was measured every two days. The mice were killed at 4 weeks after treatment, the lungs were removed and fixed in Bouin′s solution to observe the number of metastatic nodules, and tumor tissues were used for immunohistochemical examination of tumor cell proliferation and vascular density. Results The tumor formation rate was 100% in the MMTV?PyMT?positive mice. The tumor weight of LBP group was 4?208 ± 0?4463 g, significantly lower than the 6?477g ± 0?3724 g in the control group (P<0?005). The number of pulmonary nodules of the LBP group was 12 ± 1?155, significantly less than that of the control group (20 ± 2?745) (P<0?05). The immunohistochemical examination using Ki67 and CD31 staining showed that tumor cell proliferation and microvessel density of the LBP group were significantly less than the NS group. Conclusions LBP inhibits breast cancer growth and metastasis through the inhibitory effect on tumor growth and metastasis, inhibition of tumor cell proliferation and angiogenesis in MMTV?PyMT mice. These mice can be used as an ideal model for studies on antitu?mor drug development for the treatment of breast cancer lung metastasis.
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This paper described the necessity to cultivate medical students′ethical quality during clinical pro-bation teaching in gynecology and obstetrics department. Then it analyzed the ethical problems faced in clinical pro-bation teaching due to traditional social values and cultural differences. As well, it put forward to improve the whole ethical quality and clinical ethics decision-making capacity of medical students through carrying out education and communication before probation, paying attention to ethical quality training, and penetrating ethical quality training throughout each part of teaching.
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Objective To investigate the potential role of Lycium bararum polysaccharide (LBP) with or without interferon -inducible protein 10 ( CXCL10) in inducing dendritic cells ( DC) functional maturation by monitoring the alteration of cytokines for inducing DC maturation in peripheral blood and by detecting the expression of S-100 protein in tumor tissue, thus to reveal its mechanism of inhibiting experimental liver cancer. Methods H22 bearing mice model was established. The mice were randomized into model group, LBP group (50 mg/kg, ig), CXCL10 (right axillary subcutaneous injection of 15 μg/kg), LBP + CXCL10 group (LBP 50 mg/kg, ig, and right axillary subcutaneous injection of CXCL10 15 μg/kg), 5- fluorouracil (5FU) group ( intraperitoneal injection of 12mg/kg) , 12 mice in each group. The mice were administered the corresponding medicine once a day. After treatment for 2 continuous weeks, blood was sampled from infraorbital vein, and the tumor mass, spleen, thymus were extracted for the calculation of anti-tumor rate, thymus index and spleen index separately . The mRNA expression levels of interleukin 12 (IL-12) and tumor necrosis factor-α (TNF-α) in peripheral blood were detected by fluorescence quantitative PCR, the expression of S-100 protein in tumor tissues was detected by immunohistochemical assay. Results Compared with the model group, tumor growth in LBP group and LBP+CXCL10 group was obviously inhibited, and tumor-inhibitory rate was 55.90%, 50.91%, respectively. Meanwhile, the mRNA expression level of IL-12 was 2.94 folds higher in LBP group and 3.39 folds higher in LBP + CXCL10 group, and TNF-α mRNA expression level was 1.55 folds higher in LBP group and 4.74 folds higher in LBP+CXCL10 group than the model group, the differences being statistical significant ( P<0.05 or P<0.01). Results of immunohistochemical assay showed that S-100+DC number in LBP group and LBP+CXCL10 group was larger than that in the model group (P<0.05 ). Conclusion LBP and LBP+CXCL10 exert significant effect on inhibiting experimental liver cancer. The mechanism may be related with inducing the secretion of IL-12 and TNF-α, which plays a key role in inducing DC maturation, and with the increase of the number of DC in tumor microenvironment.
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Continuous medical imaging education is important for radiologists to improve their image diagnosis ability.In order to adapt to the development of medical education,the department of radiology in Tangdu hospital had built a set of teaching-picture archiving and communication system (TPACS) with its own intellectual property rights based on its own advantages.This system was actively put into use for scholar radiologists and the efficiency and quality of education as well as the development of continuous education for scholar radiologists were improved and promoted conspicuously.
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Objective To explore effective coping style of targeted psychodrama on teenager offenders.Methods Targeted psychodrama intervention procedures were designed.60 teenagers selected from juvenile detention jail were randomly divided into experimental group and control group.Psychodrama intervention was applied to the experimental group to test the changes of the two groups before and after the intervention using simplified coping style questionnaire.Results Before the intervention,the positive coping style level of the experimental group was 1.40 ± 0.42,the negative coping style level was 2.19 ± 0.32; after the intervention,the positive coping style level of the experimental group was 2.13 ± 0.36,the negative coping style level was 1.77 ±0.30.The difference of the experimental group's positive response and the negative response were significant before and after the intervention(t =-6.223,P< 0.01; t =9.749,P<0.01).The difference of the control group's positive response and the negative response were not significant (P > 0.05).Conclusion Psychodrama intervention has a positive effect on the criminal teenagers coping styles,and it can improve their social adaptability.
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0bjective To investigate the relationships between the peripheral lung cancer and pulmonary vessels or bronchi by 16-row muhislice computed tomography(MSCT)and analyze the related factors.Methods Fifty-four patients with peripheral lung cancer confirmed pathologically underwent contrast-erdaanced MSC TI Multiplanar reformation(MPR)and maximum intensity projection(MIP)in all patients were used to demonstrate the relationships between the peripheral lung cancer and pulmonary vessels,bronchi.The relationships were categorized five types:Type 1,erupted at the edge of nodule. Type 2,erupted at the center of nodule.Type 3,penetrated through the nodule.Type 4,contacting the nodule but stretched or encased.Type 5,contacting the nodule but smoothly compressed.The pathology type,stage,size,density and location of the peripheral lung cancer were recorded and the relationships with five types were evaluated by using Chi-square test and correlation analysis.Results (1)Tumor-bronchi relationship:type 1(33,61.1%)was more often seen in≥2.0 cm and solid lesions with stage Ⅱ-Ⅳ.while Type 2(14,25.9%)was often seen in<2.0 am and part-solid or non-solid lesions with stage Ⅰ.(2)Tumor-PA relationship:Type 1 was more often seen in≥2.0 am and solid lesions with stage Ⅱ-Ⅳ.while Type 2 was often seen in part-solid or non-solid lesions with stage Ⅰ.(3)Tumor-PV relationship:type 4 was the most common type(29,53.7%).Type 2(13,24.1%)was more often seen in part-solid or non-solid lesions.(4)Tumor-bronchi relationship and tumor-PA relationship had a positive correlation(r=0.5265,P<0.01).Conclusions MSCT can demonstrate the relations between the peripheral lung cancer and bronchi.PA and PV.It is useful for the differential diagnosis and prognosis evaluation of the lung csncer.
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OBJECTIVE: To study the effects of Lycium barbarum polysaccharide (LBP) on tumor microenvironment T-lymphocyte subsets and dendritic cells in H22-bearing mice and the mechanisms for intervention of tumor immune escape by LBP. METHODS: H22-bearing mice were given LBP orally for two weeks. T-lymphocyte subsets and the phenotypes of dendritic cells in tumor-infiltrating lymphocytes (TIL) were detected by flow cytometry (FCM). RESULTS: LBP could significantly increase the numbers of CD4(+) and CD8(+) T cells in TIL as compared with those in model control group (P<0.05). In model control group, the number of dendritic cells in tumor microenvironment decreased markedly, while in LBP-treated group, the increased number of dendritic cells and B7-1 expression were observed, but there were no significant differences between these two groups. CONCLUSION: LBP has anti-tumor effect probably by increasing the numbers of CD4(+) and CD8(+) T cells in TIL to relieve the immunosuppression and enhance the anti-tumor function of the immune system. But whether LBP can recover the phenocyte and function of dendritic cells in H22-bearing mice should be further studied.
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Suicide - gene therapy is now regarded as a new method for tumor with good prospect. Since bystander effect is the main mechanism and is positively correlated with the immune function, stimulating the immune function of tumor carriers and improving the inflammatory microimmune situation are two important keys to good therapeutic effect. As it is known that Chinese herbal medicine is effective in improving human immune function and has less toxic effect, therefore, suicide - gene therapy combined with Chinese herbal medicine may be a new, safe and economic regimen for tumor.
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[Objective] To investigate the effect of Lycium barbarum polysaccharide (LBP) on T-lymphocyte subsets levels, dendritic cells (DCs) counting and antigen CD80 expression in peripheral blood and tumor stroma of H22-bearing mice. [Methods] H22-bearing mice models were established. LBP in the dosages of 1.25 and 0.625 g?kg-1?d-1 was orally administered to the mice models for two weeks. The changes of T-lymphocyte subsets levels, DCs counting and antigen CDgo expression in peripheral blood and tumor stroma were detected by flow cytometry (FCM) . [ Results ] LBP increased the numbers of CD4+ and CD8+ T-cells, promoted the proliferation of CD4+ T-cells, and elevated the ratio of CD4+ /CD8+ in peripheral blood. LBP in large dosage also increased the numbers of CD4+ and CD8+ T-cells in the tumor-infiltrating lymphocytes (P
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Objective To observe the influence of Lycium Barbarum polysaccharide(LBP) on FasL expression in H22-bearing mice and to explore its anti-tumor mechanism.Methods Kunming mice were randomized into the model group,and low-and high-dose LBP(in the dose of 0.625 and 1.250 g?kg-1?d-1 respectively) groups.H22-bearing mice models were induced through right subaxillary inoculation of H22-ascitic cells.Three days after inoculation,LBP group were given LBP for 14 days.Hematoxylin and eosin(HE) staining method was used to examine the tumor cell density,tumor cell mitotic count,and lymphocyte infiltration in tumor interstitial tissue.FasL expression was observed in the three groups with immunohistochemical method.Results Tumor cell mitotic count was decreased in the two LBP groups(P
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The medium for fermentation has been selected by means of orthogonal designs. The number of cell has reached 10~(11)/ml, and spore forming rate is 70—80%. LC_(50) of mosquito larvicied is lower than 0.125 ppm. Three targets are obviously better than those of previous report. The stable results are proved by studying of fermentation in shaking flask and further in 50L~3-bench fermenter. The production cost of per ton is decreased by 33%.
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AIM: To investigate the influence and mechanisms of unsaturated fatty acid on PAI-1 expression in HepG-2 cells. METHODS: PAI-1 activity and mRNA expression were determined by colorimetric assay and RT-PCR, respectively. Two types of CAT reporter gene plasmid containing different deletions in PAI-1 promoter were constructed and transfected into HepG-2 cells, respectively. The transcriptional activity of PAI-1 was demonstrated by the CAT's expression. RESULTS: The mRNA and activity of PAI-1 significantly increased in the groups of oleic acid and linoleic acid compared with the control. When co-transfected with PPAR?-pSG5, the level of PAI-1 transcription was significantly increased. In the HepG-2 cells transfected with NF-?B-like sequence-deletion-pCAT construct linoleic acid, the PAI-1 transcriptional activity increased, and no significant change was observed when transfected with VLDL/fatty acid response element-deletion-pCAT construct. CONCLUSIONS: Unsaturated fatty acids induce PAI-1 activity and mRNA expression in HepG-2 cells. PPAR? may be one of transcription factors playing a role in the regulation of PAI-1 gene expression. The VLDL/fatty acid response element in the PAI-1 promoter may play an important role in the regulation, but not the NF-?B-like sequence.