The starting material L-tryptophan reacted with 4-chlorobenzaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the 1-(4-chlorophenyl)-beta-carboline. The intermediate was further reacted with alkyl halogenide by N(9)-alkylation and N2-quaternarization to obtain 12 novel 1-(4-chlorophenyl)-beta-carboline derivatives. The chemical structures of all target compounds were characterized by elemental analyses, MS and 1H NMR spectra. The antitumor activities of the target compounds were evaluated by MTT method. The results demonstrated that N2-quaternarized compounds enhanced the antitumor activity significantly. In particular, compound 15 was found to be the most potent compound with IC50 values lower than 5 micromol x L(-1) against 6 human tumor cells. These results confirmed that the N2-alkyl or aralkyl substituent on the beta-carboline ring played an important role in the modulation of the antitumor activities.

Background and purpose:Triple negative breast cancer (TNBC) is with high invasion, poor prognosis and lack of usefull treatment. This study investigated expression status of ICAM-1 protein in TNBC in order to explore its relationship with clinicopathological features and outcome in patients.Methods:Fifty-nine tissue samples of TNBC were collected while 50 cases of para-carcinoma tissue samples were used as negative controls. Immunohistochemical staining was conducted to detect expression level of ICAM-1 protein. The relationship of ICAM-1 protein expression with clinicopathological features (age, tumor size, subtype, grade, status of lymph node metastasis, TNM stage, vascular tumor thrombus, nerve inifltration, Ki-67, p53 and E-cadherin expression) and outcome in patients were analyzed.Results:The ICAM-1 protein expression of TNBC was signiifcantly higher than that in adjacent tissues (P=0.000). ICAM-1 expression was related to status of lymph node metastasis, grade and TNM stage (with aP-value of 0.036, 0.027 and 0.048, respectively), while demonstrated an undeifned relationship with tumor size, subtype, vascular tumor thrombus and expression of Ki-67, p53 and E-cadherin. The disease-free survival (DFS) of ICAM-1 high expression set was shorter than that of the lower one but has nothing to do with overall survival (OS). In addition, Cox proportional hazards model showed that ICAM-1 expression and lymph node metastasis were independent risk factors of DFS in patients (HR=3.2, 95%CI: 1.6 to 6.4, HR=2.7, 95%CI: 1.28 to 5.9,P<0.05).Conclusion:ICAM-1 could serve as a predictive factor for differentiation status of TNBC. The high expression of ICAM-1 in TNBC may indicate poorer prognosis.

The aging of population and the increasingly morbidity rate of chronic disease had brought great influence on public health and economy.And community whose scientific management model could improve effectivity was a main prevention place for chronic disease.Thus on the basis of domestic and foreign literatures,several types of chronic disease community management models were introduced,and aimed at providing a reference for community chronic disease management.

Objective To investigate the effect of different dose of dexmedetomidine for pre-venting the visceral traction reaction during caesarean section under spinal anesthesia.Methods Two hundred ASA physical status Ⅰ-Ⅱ patients,full-term primiparas scheduled for elective cesarean sec-tion were enrolled in this randomized,placebo-controlled study.Patients were randomly allocated to receive dexmedetomidine in four groups:group C (0.9% normal saline),group D1(dexmedetomidine 0.6 μg/kg),group D2(dexmedetomidine 0.8 μg/kg),group D3 (dexmedetomidine 1.0 μg/kg),50 cases in each group.Two minutes after cutting umbilical,groups D1,D2,D3 received an intravenous infusion single-dose of 0.6,0.8,1.0 μg/kg dexmedetomidine respectively for 10 minutes.Group C was injected the same dose of saline.Maternal blood pressure (BP),heart rate (HR),Ramsay scores,visceral traction reaction conditions were recorded at three points:before iv (T0 ),10 min af-ter iv (T1 )and abdominal exploration (T2 ).Results As for the inhibition of visceral traction pain, groups D2 and D3 were obviously better than groups D1 and C,and there was no statistically signifi-cant difference between groups D2 and D3 at T2 (P <0.05 ).The effects of slowing down heart rate and increasing blood pressure were weaker in group D2 than that in group D3 at T2 .Ramsay scores were higher in groups D2 and D3 than in groups D1 and C (P <0.05),and there was no significant difference between groups D2 and D3 at T2 .Conclusion Administration of dexmedetomidine 0.8 μg/kg could alleviate the visceral traction reaction and had little effect on maternal hemodynamics.

Cultivation of laboratory physicians in accordance with the needs of discipline should be a priority of education on laboratory medicine in China. Unfortunately, the professional career of Chinese laboratory physicians is presently entrapped in a dilemma owing to unfavorable settings, in-cluding the late start of laboratory physician training in this country, unmatched installation between higher school faculty and curriculum, faulty programs of in-hospital training, disparity in management policies, low social esteem, uncertainty in personal intention of employment, and poor knowledge of position awareness. This paper puts forward a lot of measures such as the development trend of the university curriculum, which is in compliance with the subdivision and refinement of clinical medicine, the establishment of a medical degree for a professional laboratory physician, constantly improving the standardization of laboratory physician residency training and continuing education system for the in-spection of doctors , setting up physicians inspection posts and giving a clear mandate to examine physicians inside the hospital, while outside of the hospital continually improving awareness and accep-tance of the laboratory physicians, giving more educational resources to laboratory physicians, so as to improve the overall level of the laboratory medicine.

Objective:To construct a mutant D314A of Escherichia coli cytosine deaminase (EC-CD, substitution of an alanine (A) for the aspartic acid (D) at position 314 of cytosine deaminase) and investigate its antitumor effect. Methods: Eukaryotic expression plasmid containing EC-CD gene (pcDNA3.1-CD~(wt)) was constructed, and the mutant pcDNA3.1-CD~(D314A) plasmid, with aspartic acid (D) at position 314 of EC-CD gene substituted by alanine (A) (EC-CD~(D314A)), was established by site-directed mutation. EC-CD~(wt) and EC-CD~(D314A) were transfected into human colon cancer cell line LoVo via Lipofectamine~(tm) 2000, and positive LoVo-CD~(wt) and LoVo-CD~(D314A) cells stably expressing corresponding genes were selected by G418. The cytotoxicity and bystander effects of EC-CD and EC-CD~(D314A) genes on LoVo cells were e-valuated by MTT assay. Results: The mutant D314A was confirmed by sequence analysis. EC-CD and EC-CD~(D314A) mRNA were expressed after transfected into LoVo cells. The IC_(50) of Lovo-CD~(D314A) cells was (85.13±0.60) mmol/L, which was significantly lower than that of LoVo-CD~(wt) cells ([689.76±0.45] μmol/L, P=0.000). Bystander effect assay showed that, when at the ratio of 30%, the survival rates of LoVo-CD~(wt) cells and Lovo-CD~(D314A) cells were (48.5±0.49)% and (17.3±0.40) % (P = 0.000), respectively. Conclusion: Mutatant EC-CD gene (EC-CD~(D314A)) has a significantly in-creased antitumor effect on LoVo cells compared with wild type EG-CD gene, and it may become a new candidate gene for tumor gene therapy.

Objective: To assess the expression of miR-21, miR-221, and miR-222 in exosomes of CAL27 tongue squamous cell carcinoma cells. Methods : CAL27 tongue squamous cell carcinoma cells and normal human oral keratinocytes (HOKs) were cultured, and then, the cultured supernatant was collected to separate the exosomes. Exosomes were detected by electron microscopy, and the expression levels of miR-21, miR-221, and miR-222 in the exosomes of tongue cancer cells were measured by qRT-PCR. Results: Exosomes existed in the cultured supernatants of CAL27 cells and HOKs. Additionally, the expression levels of miR-21, miR-221, and miR-222 in the exosomes of CAL27 cells were significantly enhanced compared with those in the HOK exosomes (P < 0.05). Conclusion The expression levels of miR-21, miR-221, and miR-222 were markedly enhanced in the exosomes of CAL27 tongue squamous cell carcinoma cells.

OBJECTIVE：To study the effects of berberine on mic e macrophage polarization based on TLR 4-MyD88-NF-κB signaling pathway. METHODS ：Using mice RAW 264.7 macrophage as the object ，atorvastatin calcium as positive control ， inflammatory cell model was induced by lipopolysaccharide （LPS）；ELISA method was used to detect the contents of TNF-α，IL-6 and NF-κB in cell culture medium after treated with low，medium and high doses of berberine （5，10，20 μmol/L）for 24 h. The real-time fluorescence quantitative PCR was conducted to determine the mRNA expression of TLR 4 and MyD 88 in cells. Western blotting assay was used to detect the protein expression of TLR 4，MyD88，iNOS and CD 206 in cells. RESULTS ：Compared with blank control group ，the contents of TNF-α，IL-6 and NF-κB in cell culture medium，mRNA expression of TLR 4 and MyD 88， protein expression of TLR 4，MyD88 and iNOS in cells were increased significantly in LPS induction group （P＜0.05）. Compared with LPS induction group ，the contents of TNF-α and IL-6，mRNA and protein expression of TLR 4 and MyD 88 in atorvastatin calcium group ，berberine medium-dose and high-dose groupsas well as the content of NF-κ B and protein expression of iNOS in administration groups were decreased significantly ， while the content of NF-κB in berberine high-dose group was significantly lower than atorvastatin calcium group （P＜0.05）. The protein expressions of CD206 in atorvastatin calcium group and berberine high-dose group were increased significantly ，while the protein expression of CD 206 in berberine high-dose group was significantly higher than atorvastatin calcium group （P＜0.05）. CONCLUSIONS ：Different doses of berberine can intervene in mice macrophage polarization to different extents ，the mechanism of which may be associated with the regulation of TLR4/MyD88/NF-κB signaling pathway.

Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.