Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective To investigate the expression of Toll like receptor 4(TLR4)in the injured brain tissue atter traumatic brain injury(TBI) and explore the potential role of TLR4/NF-κB in the secondary brain injury.Methods Thirty-six SD rats were randomly divided into control group(n=1 2),TBI inducement for 1 d group(n=6),TBI inducement for 3 d group(n=12)and TBI inducement for 7 d group(n=6).TBI models of the later 3 groups were induced by Feendy's free-falling,and rats of the control group are only performed exposure ofdura of the right parietal lobe.TLR4 mRNA expression in the injured brain tissue was studied by RT-PCR,NF-κB binding activity was detected by electrophoretic mobility shift assay (EMSA),and the TNF-α and IL-6 levels were detected by enzyme linked immunosorbent assay(ELISA).Immunohistochemistry was employed to determine the protein expression of TLR4 in the brain tissues of control group and TBI inducement for 3 d group.Results The TLR4 mRNA expression,NF-κB binding activity,and the levels of TNF-t and IL-6 in rats of the TBI inducement for 1,3 and 7 d groups were significantly increased as compared with those in the control group(P＜0.05).The protein expression level of TLR4 in the brain tissue of control group was rare,and a large number of TLR4-positive immunostained cells,including cortical glial cells and neurons,were noted in the brain tissue of TBI inducement for 3 d group.TLR4 mRNA level was positively correlated to the NF-κB activity(r=0.786,P=0.000),and positive relations were also noted between TLR4 mRNAlevel and both TNF-α and IL-6 levels(r=0.517,P=0.010; r=0.503,P-0.012).Conclusion TBI could induce concomitant and persistent up-regulation of TLR4 expression and NF-κB binding activity in the injured brain tissue.TLR4/NF-κB might play a central role in the secondary injury after TBl.

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin^®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin^®. BAT1706 and Avastin^® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin^® are highly similar in terms of in vitro functional activities.

OBJECTIVETo isolate MSCs from adult human bone marrow cells and to induce them into adipocytes.

METHODSMSCs were isolated from adult human bone marrow aspirated by Percoll and expanded in L-DMEM. The surface antigen of MSCs, CD14, CD34, CD45, CD44, VLA-1, HLA-DR and cell cycle were analysed on a FACScan flow cytometer. MSCs were cultured in adipogenisis inducing medium including insulin, 1-methyl-3-isobutylxanthine, indomethine and dexamethasone for 7 days and stained with Oil Red O.

RESULTSMSCs grew as adherent cells and expanded more than 10 passages. They were positive for CD44 and negative for CD14, CD34, CD45, HLA-DR. The expression of VLA-1 was weak. After 7 days of adipocyte inducing, about 85%of the cells displayed accumulation of lipid vacuoles, as detected by Red Oil O.

CONCLUSIONMSCs isolated and cultured from adult human bone marrow can be induced to adipogenisis committed differentiation.

Adipocytes ; physiology ; Adult ; Antigens, CD34 ; analysis ; Bone Marrow Cells ; physiology ; Cell Differentiation ; Cell Separation ; methods ; Cells, Cultured ; HLA-DR Antigens ; analysis ; Humans ; Hyaluronan Receptors ; analysis ; Lipopolysaccharide Receptors ; analysis ; Stem Cells ; physiology

OBJECTIVEThis study investigates the efficacy and tolerability of capecitabine plus thalidomide in patients with advanced pancreatic cancer who previously underwent gemcitabine-based therapy.

METHODSSixty-one patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen were enrolled. The patients were randomly divided into two groups. One group (31 patients) was treated with capecitabine alone, and another group was treated with capecitabine plus thalidomide. Capecitabine was administered orally twice a day at a dose of 1, 250 mg/m(2) for 14-day followed by 7-day rest and oral thalidomide 100 mg was given daily without interruption until disease progression or occurrence of unacceptable toxicity.

RESULTSThe PFS was 2.8 months (95%CI 2.4 - 3.2) vs. 3.1 months (95%CI 2.6-3.6, P < 0.05) and the OS was 6.1 months (95%CI 5.3 - 6.9) vs. 6.3 months (95%CI 5.2 - 7.4, P = 0.426). In the capecitabine alone group, one patient experienced a partial response (PR), 10 patients showed stable disease (SD) and 20 patients had progressive disease (PD). The another group, two patients experienced a partial response (PR), 11 patients SD, and 17 patients PD. The disease control rates were 35.5% and 43.3%, respectively. The major adverse reaction in the two groups was grade 3 diarrhea.

CONCLUSIONCapecitabine plus thalidomide regimen is marginally effective and well tolerated in the second-line setting in patients with gemcitabine-refractory advanced pancreatic cancer.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms ; drug therapy ; pathology ; Remission Induction ; Survival Rate ; Thalidomide ; administration & dosage ; adverse effects

OBJECTIVETo analyze and summarize the clinical and pathological characteristics of intracranial haemangioblastoma and to improve surgery effect.

METHODSeventy-two patients with intracranial haemangioblastoma who were proven by operation and pathology from 1970 to 1988 were analyzed retrospectively.

RESULTSIntracranial haemangioblastoma tends to occur in the hemisphere of cerebellum (83 tumours, 87%) and the age of them ranged from 20 to 40 years (47 cases, 58.3%) mostly. The ratio of men (46 cases) was higher than women (26 cases). The diagnosis of the disease depends on CT and MR substantive haemangioblastoma. The most effective and reliable treatment of intracranial haemangioblastoma is surgical resection.

CONCLUSIONIntracranial haemangioblastoma is benign tumour which can be, cured by total surgical resection. The key recurrence factors include the young age of initial onset, mistaken exploration and incomplete extirpation of tumour.

Adolescent ; Adult ; Brain Neoplasms ; pathology ; surgery ; Child ; Female ; Hemangioblastoma ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo establish a mouse model of biliary obstruction.

METHODSSixty-four Balb/c mice were divided into experimental group and control group. Obstructive jaundice was induced in the mice in the experimental group by common bile duct ligation. The level of the common bile duct diameter, WBC, LYM MID, LYM%, MID% and ALT, AST, TBIL, DBIL, IBIL, ALP and CHOL were measured 12 h and 1, 2 ,3, 4, 5, and 7 days after the ligation. The morphological changes in the liver were also observed.

RESULTSThe level of common bile duct diameter, WBC, LYM, MID, LYM%, MID% and ALT, AST, TBIL, DBIL, ALP and CHOL all underwent changes with time following certain patterns.

CONCLUSIONThe jaundice manifestation of this model is similar to that of patients with biliary obstruction, and this model may provide a reliable model for studying the mechanism of obstructive jaundice.

Animals ; Cholestasis, Extrahepatic ; pathology ; Common Bile Duct ; pathology ; surgery ; Disease Models, Animal ; Female ; Ligation ; Liver ; pathology ; Mice ; Mice, Inbred BALB C

In this text the interface of hardware and software for laboratory analyzer is analyzed. Adopting VC++ and multi-thread technique, the real-time communication without errors between LIS and the laboratory analyzer is realized. Practice proves that the system based on the technique is stable in running and all data are received accurately and timely.
Clinical Laboratory Information Systems ; Computer Systems ; Software Design ; User-Computer Interface

OBJECTIVETo observe the changes of telomere length and telomerase activity in patients with aplastic anemia (AA), and relationship with immunosuppressive therapy (IST) efficacy, to explore the pathogenesis of AA and the role of telomere length in evaluating immunosuppressive therapy efficacy.

METHODS71 cases of AA patients between September 2010 and March 2013 were enrolled into this study. 3 ml peripheral blood specimens from this cohort of patients were collected to test the telomere length in peripheral blood mononuclear cell (PBMNC) with flow-FISH and detect telomerase activity with TRAP-PCR-ELISA method.

RESULTSTelomere length and age showed negative correlation (b=-0.387, P=0.001) in normal control, NSAA and SAA + VSAA groups, telomere length became shorter with the growth of age, and normal control group telomere length decreased along with the age growth slightly greater than the other two groups (NSAA, SAA+VSAA). Besides the effect of age on telomere length, no significant difference was observed between NSAA and SAA+VSAA groups (P=0.573), and NSAA, SAA+VSAA (30.957 ± 4.502,29.510 ± 5.911)groups were significantly shorter than normal control group (51.086±10.844) (P<0.01). Telomere length in NR group (25.357±4.848)was significantly lower than normal control group (51.086 ± 10.844) (P=0.005), telomere length in CR(32.808 ± 4.685)/PR groups (30.334±4.464) compared with normal control group had no significant difference (P=0.517, P=0.254). Telomere length below 29.21% obviously decreased outcomes of IST. Telomerase activity had significant difference (χ²=20.385, P<0.01). The telomerase activity had no significant difference in terms of age and gender in three groups, multiple comparison found that telomerase activities in SAA + VSAA (0.324±0.178) (P<0.01), and NSAA (0.234±0.175) groups (P=0.002) were significantly higher than normal control group (0.107±0.083).

CONCLUSIONTelomere length of PBMNC in AA patients was significantly shortened than normal control group with telomerase activity increased, and telomere shorted more apparently in NR group, these patients should adjust the treatment as early as possible. Telomeres could predict the curative effect of IST.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; enzymology ; therapy ; Case-Control Studies ; Child ; Female ; Humans ; Immunosuppression ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Telomerase ; metabolism ; Telomere ; metabolism ; Treatment Outcome ; Young Adult

BACKGROUNDSpinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.

METHODSIn this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.

RESULTSWe found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.

CONCLUSIONSCollectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.

Adult ; DNA Repeat Expansion ; genetics ; Female ; Humans ; Machado-Joseph Disease ; genetics ; pathology ; Male ; Mutation ; genetics ; Spinocerebellar Ataxias ; genetics ; pathology ; Trinucleotide Repeat Expansion ; genetics