The effect of colored noise on circadian oscillation and internal signal stochastic resonance(ISSR) has been studied in a Neurospora circadian clock system. The result shows that the correlation time of colored noise can affect strongly the strength of ISSR. For the case of no external signal(ES), the correlation time of colored noise plays a suppressive role for ISSR, and the suppressive role is increased with the increment of correlation time of colored noise. When the ES is injected to the system, with the increasing of the correlation time of colored noise, not only its suppressive role for ISSR is increased, but also the single peak ISSR can be transformed as internal single stochastic bi-resonance (ISSBR). There exists an optimal frequency of ES for the ISSR information amplification, while the ISSR is suppressed for another frequency of ES. In contrast to external colored noise, internal colored noise is more efficient to sustain and amplify the ISSR information. Furthermore, there exists a critical noise intensity for destroying the difference between white and colored noises.

Objective To investigate the anticancer activity of dendritic cells(DC)transfected by recombinant adeno-associated virus(rAAV)-mediated carcinoembryonic antigen(CEA)gene in colorectal cancer treatment.Methods The recombinant plasmid rAAV/CEA was constructed and the rAAV/CEA virus stock was prepared.DC precursors were isolated from peripheral blood mononuclear cells(PBMC)by density gradient centrifugation and transfected with rAAV/CEA virus stock.The CEA expression,chromosome integration and efficiency of rAAV/CEA virus were determined by PCR,Southern blot and flow cytometery.DC precursor cells were induced by granulocyte macrophage colony-stimulating factor(GM-CSF),interleukin-4(IL-4)and tumor necrosis factor-?(TNF-?)to mature DC.The mature DC and T cells were mixed,then cultured with interleukin-2(IL-2)and interleukin-7(IL-7)resulting in generation of cytotoxic T lymphocyte(CTL),whose lethal effects on cancer cells were determined by 51chromium(51Cr)release assay.3H incorporation method was employed to detect the influence of rAAV/CEA transfected DC in the proliferation of activated T cells.Results rAAV medicated CEA gene was transferred into DC precursor successfully and the expression was high.Over 90% DC precursors expressed CEA protein.The viral gene was integrated into the DC chromosome.rAAV/CEA transfected DC could induce specific CTL which could specifically recognize and kill CEA-positive colorectal cancer LoVo cell line,and showed restrictive activity of anti-MHC class I antigen,while it was not able to kill the CEA-negative cancer cells.Conclusion The present study confirms that rAAV/CEA transfected DC vaccine can induce anti-tumor activity in vitro.It paves the way for further study on CEA as a target antigen for gene therapy on colorectal cancer.

Objective To evaluate the antineoplastic effect of laser immunotherapy in mice with multiple cutaneous squamous cell carcinoma (CSCC).Methods Normal immunocompetent hairless SKH-1 mice were consecutively irradiated by ultraviolet rays to establish mouse models of multiple CSCC.Then,20 CSCC-bearing mice were randomly and equally divided into 4 groups:laser group irradiated with an 808-nm near-infrared laser (1 W/cm2,10 minutes) once every two weeks for a total of 3 sessions,laser immunotherapy group irradiated with an 808-nm nearinfrared laser as above and topically treated with imiquimod cream once a day for 3 days before and after each session of irradiation,imiquimod group treated with imiquimod cream as in the laser immunotherapy group,and control group receiving no treatment.The volume of tumors was calculated,and their morphology as well as the survival of mice were observed after the treatment.The t test and Mantel-Cox log-rank test were used to compare the volume of tumors on the dorsum and survival rates of mice,respectively,on days 27 and 60 after the start of treatment.Another 12 CSCC-bearing mice were randomly and equally divided into the 4 groups mentioned above,and tumor tissues were resected from these mice for histopathological examination on day 5 after the first treatment.Results On day 27,the volume of tumors significantly increased in the control group and imiquimod group (both P ＜ 0.05),but experienced no significant increase in either of the other two groups compared with that before the start of treatment (both P ＞ 0.05).Moreover,the volume of tumors in the control group was slightly larger than that in the imiquimod group (P ＞ 0.05),but significantly larger than that in the laser group and laser immunotherapy group (both P ＜ 0.05).The volume of tumors in the laser group increased,and was significantly larger than that in the laser immunotherapy group on day 60 (P ＜ 0.05).Mice all died within 40 days in the control group,and within 50 days in the imiquimod group;one mouse died on days 52 and 53 separately,and the other mice all survived longer than 60 days in the laser group;no mice died within 60 days in the laser immunotherapy group.By day 60,the survival time of mice was slightly longer in the imiquimod group (P ＞ 0.05),significantly longer in the laser group and laser immunotherapy group compared with the control group (both P ＜ 0.05),but similar between the laser group and laser immunotherapy group (P ＞ 0.05).Histopathological examination showed that 5-day topical application of imiquimod cream did not cause death of tumor cells,but numerous tumor cells died in the laser group and laser immunotherapy group.Multiple inflammatory cells were observed around the tumors,and the number of the inflammatory cells was obviously larger in both the laser group and laser immunotherapy group,especially in the latter group,compared with the control group.Conclusion Laser immunotherapy is a new effective and safe treatment for CSCC in mice,and has potential value especially in the treatment of multiple or metastatic CSCC.

ObjectiveTo compare the clinical value of contrast-enhanced ultrasonography (CEUS) and conventional ultrasonography in diagnosing polypoid lesion of gallbladder (PLG).MethodsThe postoperative pathology and clinical manifestation of 49 PLG patients were retrospectively analyzed in the First Afifliated Hospital of Harbin Medical University. Of them, 7 cases were maligant lesions, 4 cases were adenomas, 24 cases were polyps of gallbladder and 14 cases were adenomyomatosis of gallbladder. With postoperative pathology as golden standard, the sensitivity, speciifcity and PLG speciifcity were calculatedfor conventional ultrasonography, CEUS and conventional ultrasonography plus CEUS.ResultsThe sensitivity, specificity and PLG specificity were 33.3%, 74.3% and 68.3% for conventional ultrasonography, and 66.7%, 85.7% and 82.9% for CEUS respectively. The conventional ultrasonography plus CEUS were 83.3%, 88.6% and 87.8%.ConclusionCEUS could signiifcantly improve the diagnostic accuracy.

According to the constructivism approach, instructors have to adapt to the role of fa-cilitators but not teachers. Whereas a teacher gives a didactic lecture that covers the subject matter , a fa-cilitator helps the learner to get to his or her own understanding of the content. In the former scenario the learner plays a passive role and in the latter scenario the learner plays an active role in the learning pro-cess. Under the guidance of this theory, a multi-dimension teaching model based on classroom teaching, network platform and innovate experiments has been established in the course of basis of clinical labora-tory. It has been found that this model is conducive to raising students' interests in learning and to culti-vating student's comprehensive quality.

Objective To observe the effects of Yiqi Huoxue Tongluo Jiedu fang (YHTJF) on pneumocyte apoptosis after lung ischemia/reperfusion (I/R) injury (LIRI) in mice and to investigate whether c-Jun N-terminal protein kinase (JNK) is involved in the mechanism of apoptosis.Methods Seventy C57BL/6J male mice were randomly divided into seven groups:normal control group (C group),carboxyl methyl cellulose-Na+normal control group (CMC-Na+C group),CMC-Na+sham group (CMC-Na+S group),CMC-Na+I/R group (CMC-Na+I/R group) and CMC-Na+YHTJF-low,-middle,-high dose groups (CMC-Na+YL,CMC-Na+YM,CMC-Na+YH groups).C group did not undergo any processing;in CMC-Na+S group,only was chest opened without clipping the lung hilum;in the rest of the four groups,they all underwent opening of the chest and clipping the lung hilum for 30 minutes,then the clipping of artery was relieved and left lung reperfusion was carried out for 3 hours.After operation,the mice were sacrificed,the lung tissues were harvested.Under light and electron microscopes,the lung morphological and ultra-structural changes were observed,and the changes of index of quantitative evaluation for alveolar damage (IQA) were determined.The terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was applied to evaluate the apoptosis index (AI) of the lung tissues.The protein and mRNA expressions of JNK and glucose regulating protein 78 (GRP78) in lung tissues were detected by Western Blot and reverse transcription-polymerase chain reaction (RT-PCR);the correlations between lung AI and the expressions of mRNA and protein of JNK and GRP78,IQA were analyzed.Results Compared with CMC-Na+S group,IQA,AI and mRNA and the protein expressions of JNK and GRP78 in CMC-Na+I/R group were obviously higher [IQA:(74.00 ± 7.31)％ vs.(7.00 ± 1.23)％,AI:(64.40 ± 11.97)％ vs.(5.60 ± 1.14)％,JNK mRNA (gray value):1.143 ± 0.284 vs.0.152 ± 0.128,GRP78 mRNA (gray value):0.897 ± 0.129 vs.0.284 ± 0.044,JNK protein (A value):0.428 ± 0.074 vs.0.073 ± 0.052,GRP78 protein (A value):1.075 ± 0.145 vs.0.589 ± 0.060].Compared with CMC-Na+I/R group,the IQA,AI,protein and mRNA expressions of JNK and GRP78 in CMC-Na+YL,CMC-Na+YM,CMC-Na+YH groups were all lower,and the degree of reduction in group CMC-Na+YM was the most remarkable,greater than that in CMC-Na+YL or CMC-Na+YH group [IQA:(26.20 ± 3.35)％ vs.(34.00±5.34)％,(41.20±9.18)％,AI:(29.40±3.05)％ vs.(48.20±3.83)％,(39.20±6.14)％,JNK mRNA (gray value):0.681 ± 0.130 vs.0.804 ± 0.153,0.938 ± 0.11,GRP78 mRNA (gray value):0.450 ± 0.105 vs.0.747 ± 0.231,0.566 ± 0.115,JNK protein (A value):0.188 ± 0.049 vs.0.261 ± 0.065,0.209 ± 0.063,all P ＜ 0.01],compared with the CMC-Na+I/R group,the expression of GRP78 protein was obviously higher in CMC-Na+YH,CMC-Na+YL,CMC-Na+YM groups and the most remarkably high was in CMC-Na+YH group (A value:1.429 ±0.226 vs.1.130±0.169,1.128 ±0.177,all P ＜ 0.01).The apoptosis of each group was mainly in the pulmonary vascular endothelial cells and alveolar epithelial cells,and brown particles were positive cells under light microscope.Under transmission electron microscope:nuclear pyknosis and margination under the nuclear membrane,cytoplasm condensed,lamellar bodies decreased and emptying increased,cell membrane microvilli decreased or disappeared,mitochondria swelling,inflammatory cells increased in alveolar septum and adhering onto the capillary walls could be seen in CMC-Na+I/R group.Compared with CMC-Na+I/R group,the lung tissue ultrastructural damage alleviated,ultrastructure of alveoli clearly seen,nuclear chromatin relatively uniform,cytoplasm increased,type Ⅱ alveolar epithelial cell surface microvilli relatively plenty,lamellar corpuscle number increased,mitochondria swelling ameliorated in CMC-Na+YH,CMC-Na+YL,CMC-Na+YM groups and the most remarkable one was CMC-Na+YM group.AI was significantly positive correlated with the mRNA and protein expressions of JNK,GRP78 and IQA (r =0.907,0.928,0.880,0.712,0.911,all P ＜ 0.01).Conclusions YHTJF may effectively alleviate the cell apoptosis in mice LIRI,and its mechanism may be related to the inhibition of JNK pathway.

There are many kinds of artifacts in image series of functional MRI, such as head motion artifacts, physiological motion artifacts, blood flow artifacts, ghost artifacts and susceptibility artifacts. These artifacts which are unassociated with the neural activities, have so severe affects on the analysis of functional MRI data that they not only reduce the sensibility and reliability of functional MRI, but also make the detecting, locating and visualizing of the functional active regions more complicated. The mechanism and the effect of artifacts in functional MRI are discussed here, the methods of correcting artifacts are reviewed, and research prospects are discussed too.
Artifacts ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging ; methods

The main clinical symptoms of Parkinson's disease (PD) are resting tremor, muscle rigidity, bradykinesia, and so on. There is no effective treatment for PD yet, and dyskinesia symptoms affect the life qualities of PD patients. The therapy used for reinforcing kidney and activating blood circulation in treatment of PD can achieve good clinical effects.

BACKGROUND:Anticancer drug and organic metal complexes wil form a new structure or a change in ion concentration, thus changing both the activity and toxicity to produce a synergistic effect. OBJECTIVE:To synthesize new high-efficient and low-toxic metal-fluorouracil complexes as anticancer drugs. METHODS:Copper, zinc and iron salts and fluorouracil were used to synthesize four copper, zinc and iron-fluorouracil complexes that were [Cu(5-Fu)2Cl2], [Cu(5-Fu)2(NO3)2], [Fe(5-Fu)3]SO4 and [Zn(5-Fu)2Cl2]. Preliminary chemical structures of the four complexes were confirmed by elemental analysis and mass spectrometry. Their inhibitory activity on human cancer cells, human leukemia cellline K562 and human colon cancer cellline HCT-116, was measured by MTT colorimetric assay. RESULTS AND CONCLUSION:[Cu(5-Fu)2Cl2], [Cu(5-Fu)2(NO3)2], [Zn(5-Fu)2Cl2] and [Fe(5-Fu)3SO4] were successful y synthesized. These four complexes at a mass concentration of 0.1-100 mg/L inhibited the proliferation of K562 and HCT-116 to different extents. The IC 50 values of these four complexes on K562 and HCT-116 cells were lower than those of fluorouracil, and their cytotoxicity was 1.5-7.8 times higher than that of fluorouracil. To conclude, copper/iron/zinc-fluorouracil complexes exhibit synergic inhibitory effects on cancer cellproliferation.

Objective To assess the therapeutic effect of plum-blossom needle tapping combined with topical imiquimod immunotherapy on cutaneous squamous cell carcinoma (SCC) in SKH-1 mice,and to explore the immunological mechanism.Methods A total of 40 SKH-1 mice with ultraviolet light-induced cutaneous SCC were randomly and equally divided into 4 groups:control group receiving no treatment,plum-blossom needle group receiving plum-blossom needle tapping on all the tumors once a day,imiquimod group topically treated with imiquimod 5％ cream at a dose of 1.2 g/kg once a day,combination group firstly treated with plum-blossom needle tapping on all the tumors,and after the stop of bleeding topically treated with imiquimod 5％ cream at the same dose as the imiquimod group once a day.All the mice were treated for 30 days.Morphological changes of tumors in all groups were photographed and recorded every day.The tumor size was measured once every three days,and changes of total tumor volume and survival rate of the mice were compared among the 4 groups.At the end of treatment,tunor tissues were resected,and histopathological changes were compared among the 4 groups.Real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to measure the mRNA expression of interferon-α (IFN-α),IFN-β,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-o) and IL-12 in tumor tissues.Results In the combination group,tumors on the back of mice grew slowly,and some even regressed.However,tumors grew fast in the control group,plum-blossom needle group and imiquimod group,and grew more slowly in the plum-blossom needle group and imiquimod group than in the control group.Before the treatment,there was no significant difference in the total tumor volume among the 4 groups (F =0.90,P ＞ 0.05).After 24-day treatment,the total tumor volume significantly differed among the 4 groups (F =5.16,P ＜ 0.05).The LSD-t test showed that the total tumor volume significantly decreased in the combination group compared with the control group (P ＜ 0.01),but no significant difference was observed among the other groups (P ＞ 0.05).Log-rank test revealed that survival curves significantly differed among the 4 groups (x2 =8.32,P ＜ 0.05).The survival rate was significantly higher in the combination group than in the control group (x2 =4.62,P =0.03),but did not differ between the plum-blossom needle group or imiquimod group and the control group or combination group (all P ＞ 0.05).Histopathological examination showed atypical cells arranged closely,a large number of tumor cells and some keratin pearls in the control group and plumblossom needle group,few dead tumor cells in the imiquimod group,and plenty of dead tumor cells,mild nuclear atypia and increased keratinization in the combination group.qRT-PCR revealed that the relative mRNA expression levels of IFN-α,IFN-β,IL-12,IL-1β and TNF-α were significantly higher in the combination group than those in the control group,plum-blossom needle group and imiquimod group (P ＜ 0.05).The imiquimod group showed significantly higher mRNA expression of IL-1β than the control group (P ＜ 0.01),but no significant differences were observed among the other groups (P ＞ 0.05).Conclusion Plum-blossom needle tapping can effectively enhance the anti-SCC activity and immunological effects of imiquimod in SKH-1 mice.