0.05)and the TNM staging (P=0.55).A mild elevated compared other pathological classification was found in small cell lung cancer (0.191?0.275).Conclusions The results showed that RFQ-PCR was suitable for measurement of the mRNA level of PLKI in bronchoscopic bioptic specimens.This study suggest elevated expression of PLK1 might play a important role in development of lung cancer,so that PLK1 might be a potential tumor marker for Lung cancers.Advanced studies will be needed to clarify that PLKI mRNA level do not relate to TNM staging and pathological classification.

OBJECTIVETo observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway.

METHODSNB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes.

RESULTSMAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01).

CONCLUSIONMAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.

Alkaloids ; Antineoplastic Agents ; Cell Differentiation ; Cell Line, Tumor ; Down-Regulation ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; Phospholipid Transfer Proteins ; metabolism ; Quinolizines ; RNA, Messenger ; Signal Transduction ; Tretinoin ; Tumor Cells, Cultured ; Up-Regulation

Purpose To explore the accuracy of ALK fused gene expression by immunohistochemistry ( IHC) in non-small cell lung cancer ( NSCLC) patients, and to investigate the clinical and pathological features of ALK-positive NSCLC patients. Methods By u-sing rabbit monoclonal D5F3 antibody, ALK IHC was performed on 234 NSCLC patients. ALK positive cases were confirmed by reverse transcription-polymerase chain reaction ( RT-PCR) . Results The positive incidence of ALK by IHC in 234 NSCLC specimens was 8. 97% (21/234), the positive rate of ALK fused gene verificated by RT-PCR was 5. 98% (14/234). There was significant difference with histological type, age, stage (P<0. 05), but no significant difference with gender, smoking history, tumor differentiation. Of 21 cases of ALK-positive NSCLC patients, the consistency of IHC and RT-PCR was 0 when IHC was ( +) , however, when IHC was or immunohistochemical score was >120, the consistency rate was 100%. Conclusion Although immunohistochemical expres-sion of ALK fused gene may have a certain false positive, IHC or immunohistochemical score> 120 show very high value for ALK fused gene RT-PCR followed by ALK immunohistochemistry in lung cancer is a economical and feasible method for the valuation of ALK fused gene.

OBJECTIVETo study the effect of tea polyphenols (TP) on the apoptosis of germ cells in rats with experimental varicocele.

METHODSThirty-two adolescent male Wistar rats were randomly and equally divided into groups A (sham-operation), B (high-dose TP), C (low-dose TP), and D (experimental left varicocele). Experimental varicocele was induced by partial ligation of the left renal vein in the latter three groups of rats. The animals in groups A and D were fed with normal saline, while those in B and C with TP at 40 and 10 mg per kg per d, respectively, all for 4 weeks. Then, all the rats were sacrificed and the left testes harvested for determination of the expression of HIF-1, Bcl-2, Bax, CytC, and caspase-3 by immunohistochemistry and measurement of the apoptosis index (AI) of spermatogenic cells.

RESULTSThe expression of Bcl-2 was higher in groups B and C than in D but lower than in A (P < 0.05), and lower in C than in B (P < 0.05). However, the expressions of HIF-1, Bax, CytC, and caspase-3 were lower in groups B and C than in D but higher than in A (P < 0.05), and higher in C than in B (P < 0.05). The AI of spermatogenic cells was the lowest in group A, higher in D than in the other groups but lower in B than in C (P < 0.05).

CONCLUSIONTP can reduce the apoptosis of spermatogenic cells in a dose-dependent manner in varicocele rats.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; Cytochromes c ; metabolism ; Dose-Response Relationship, Drug ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Ligation ; Male ; Polyphenols ; administration & dosage ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Renal Veins ; Spermatozoa ; drug effects ; Tea ; chemistry ; Testis ; metabolism ; Varicocele ; complications ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.

METHODSThe clinical data of 2173 consecutive early-stage breast cancer patients treated by surgery treatments were retrospectively reviewed in order to clarify the indications and contraindications of different modalities. Therapeutic outcome of different surgical treatment modes were compared in terms of recurrence-free survival ( RFS) , disease-free survival ( DFS) , overall survival (OS). The cosmetic results of breast conservation and reconstruction were also evaluated .

RESULTSThe median age of these patients was 51 years ranging from 18 to 91. Of 2173 patients, 547 had stage 0- I lesions and 1626 stage II , and 1155 (53. 2% ) premenopausal. The proportion of patients who received radical surgery, breast conservation and reconstruction after mastectomy was 83. 6% (1817/2173), 10. 5% (229/2173) and 2. 5% (55/2173) , respectively. Younger and premenopausal patients prefer conservative and reconstructive surgeries, which are reasonable for stage 0-I and non-invasive breast cancer patients. Conservative surgery was not suitable for Paget's disease of breast (P = 0. 004) , mastectomy followed by reconstruction in this type of cancer was up to 38. 5%. The recurrence and metastasis rate of conservation or mastectomy were similar with a comparable 3-year RFS of 97. 4% and 95. 4% , respectively; there were also no significant differences in RFS(P =0. 2435) , DFS( P =0. 1395) and OS(P =0. 9406) after having been followed for 3 to 64 months. Similarly, immediate reconstruction did not show any negative effects with only 1 recurrence and 1 metastasis. Aesthetic outcomes were assessed as excellent or good in 90. 0% of breast conservation surgery, and the acceptability of reconstruction was 94. 5%.

CONCLUSIONBreast conserving surgery not only has comparable survival as mastectomy, but also has better cosmetic outcomes. Immediate breast reconstruction can be a suitable option without compromising survival. It is very important in the management for early breast cancer by selecting the most suitable surgery mode for every individual patient not only to cure her disease but also to satisfy the patient psychologically. Conservation should be preferred prior to reconstruction whenever possible.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; surgery ; Carcinoma, Ductal, Breast ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paget's Disease, Mammary ; pathology ; surgery ; Reconstructive Surgical Procedures ; Retrospective Studies

OBJECTIVETo evaluate the time-effect of silica on the expression of lung tissue nitric oxide synthase (NOS) in early inflammatory damage stage of silicotic rat.

METHODSAnimal models were established by direct tracheal instillation of silica into rat lungs. Total NOS and induced NOS (iNOS) activities in bronchoalveolar lavage fluid (BALF) were assayed. The expression of iNOS protein in paraffin-embedded lung sections with Streptavidin/peroxidase (SP) immunohistochemistry were measured by tissue microarray and Image-Pro Plus.

RESULTSMost of the expression of iNOS was in the cytoplasm of macrophages and neutrophils. iNOS integrated optical density (IOD) of lung tissue increased 1.47 x 10(5) and 2.73 x 10(5) more respectively in silicatreated rats 3, 7 days after exposure than in control rats (P < 0.05), and decreased 1.11 x 10(5) more 28 days after exposure (P < 0.01). The activities of iNOS in BALF increased by 0.86, 1.89 and 0.92 U/ml respectively 3, 7, 14 days after exposure (P < 0.05 or P < 0.01). The activities of total NOS in BALF increased by 1.43, 2.05, 2.61 and 2.19 U/ml respectively 1, 3, 7, 14 days after exposure (P < 0.05 or P < 0.01).

CONCLUSIONAfter silica instillation, the iNOS-positive cells in rat lung tissue were mostly macrophages and neutrophils. There is a parabolic changing trend in the level of expression of lung iNOS during 1 - 28 day exposure to silica.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Female ; Immunohistochemistry ; Lung ; drug effects ; enzymology ; Male ; Models, Animal ; Nitric Oxide Synthase ; analysis ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity

BACKGROUNDConstruction of replication-deficient recombinant adenovirus expressing gag-pol and env genes of human immunodeficiency virus (HIV) in mice.

METHODSgag-polDelta and gp140TM genes were cloned into shuttle vector pAdTrack-CMV respectively, and then the plasmids containing gag-polDelta or gp140TM gene were cotransformed with the backbone of adenovirus into E.coli BJ5183. Transfections of the recombinants were performed to obtain recombinant adenoviruses. Its immunogenicity was evaluated by testing antibody levels of mice primed with DNA vaccines and boosted with recombinant adenoviruses.

RESULTSThe replication-deficient recombinant adenovirus could express Gp140TM, Gag P55 and P24 proteins correctly. The mice primed with DNA vaccines and boosted with recombinant adenoviruses elicited high titer of HIV-1-specific antibody compared with that inoculated with DNA vaccines only.

CONCLUSIONReplication-deficient recombinant adenovirus expressing gag-polDelta and gp140TM can elicit high titer HIV-1-specific antibodies.

AIDS Vaccines ; immunology ; Adenoviridae ; genetics ; Animals ; Female ; Fusion Proteins, gag-pol ; biosynthesis ; genetics ; Gene Products, env ; biosynthesis ; genetics ; HIV-1 ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Recombination, Genetic ; Transfection ; Vaccines, DNA ; immunology ; env Gene Products, Human Immunodeficiency Virus

Parkinson's disease is a common neurodegenerative disease in middle-aged and elderly people, in which the pathogenic factors are not yet clear. Genetics, dietary habits, environmental toxins, immunological abnormalities, inflammation and oxidative stress response, apoptosis, and mitochondrial dysfunctions which caused by a variety of physiological and biogenic changes are likely to exacerbate the occurrence of Parkinson's disease. In recent years, studies have shown that the activity of microglia is closely related to Parkinson's disease, and that the active microglia can promote the release of inflammatory factors, while the differentiation of dopamine neurons in the substantial nigra of midbrain area is also closely related to Parkinson's disease. As a histone H3K27me3 demethylase, JMJD3 is involved and affects the activity of microglia, which can regulate the polarization of microglia as well and affect the survival of dopaminergic neurons in the mesencephalon. This provides new methods and strategies for treating Parkinson' s disease. This paper summarizes the structure and function of JMJD3, as well as its role in neuro-inflammation mediated by microglia and its effect on neurons, and explores the functions and related research progress of JMJD3 in Parkinson's disease.

Objective To clarify the effect of histamine H4 receptor antagonist, JNJ 7777120, and histamine H1 receptor antagonist, Loratadine, on allergic rhinitis ( AR) in rats and to study the role of histamine H4 receptor antagonist and histamine H1 receptor antagonist in the pathogenesis of allergic rhinitis and therapeutic value of their antagonist. Methods AR animal model were induced by ovalbumin ( OVA) in the Wistar rats, which treated with histamine H4 receptor antagonist and (or) histamine H1 receptor antagonist. The allergic symptoms (sneezing and nasal rubbing) , serum total IgE and the levels of cytokines in serum or nasal lavage fluid were measured, the diversity between two groups were observed. Statistical analysis was performed using a SPSS 13. 0 software. Results Compared with AR group with no treatment, the inhibition of nasal symptoms ( P < 0. 01), a significant decrease in the levels of IgE, IL-4 in serum and Eotaxin in nasal lavage fluid(P <0. 01), a significant increase in the levels of IFN-μ in serum(P <0. 01 ) after treatment was found. Compared with group treated with Loratadine, inhibition of nasal symptoms (q value were 3.72, 4. 16, P < 0. 01), a significant increase in the levels of IgE and IL-4 in serum (q value were 8. 01, 4. 96, P <0. 05) , a significant decrease in the levels of IFN-γ in serum( q =3. 18, P <0. 05) ingroup treated with JNJ 7777120 also,but no significant differences in the levels of Eotaxin in nasal lavage fluid(P > 0.05). Administration of JNJ 7777120 and Loratadine jointly, neither additive effect nor synergistic action were found ( P > 0. 05). Conclusions Histamine H4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis, the same as histamine H1 receptor. Histamine H4 receptor antagonist, JNJ 7777120, could relieve symptoms and inflammatory conditions in allergic rhinitis, the effect was weak compared with Loratadine. Neither additive effect nor synergistic action were found between them.

OBJECTIVETo determine whether the blood pressure (BP) response to hydrochlorothiazide (HCTZ) was associated with the angiotensin converting-enzyme (ACE) I/D and aldosterone synthase (CYP11B2)-344T/C polymorphisms.

METHODSThe BP response to HCTZ 12.5 mg once daily for 6 weeks was assessed in 829 subjects with mild or moderate essential hypertension, and compared across the ACE and CYP11B2 genotypes.

RESULTSOf the 829 enrolled subjects, 785 completed the study. The systolic BP response differed according to the ACE (DD 9.4 +/- 15.7 mm Hg, ID 4.8 +/- 16.3 mm Hg, and II 5.1 +/- 14.8 mm Hg, P < 0.01), but not the CYP11B2 genotype (P > 0.05). Subjects with the combination of ACE DD and CYP11B2 CC genotypes tended to have a more pronounced systolic BP reduction than the other genotypic combinations of these 2 genes. Multiple linear regression analyses showed that the ACE DD genotype and serum aldosterone concentration at baseline were associated with the systolic BP reduction after treatment. None of the genetic associations with changes in diastolic BP or mean arterial pressure reached statistical significance (P > 0.05).

CONCLUSIONSThe present study suggested that the ACE DD genotype was associated with the systolic BP response to HCTZ, and that the subjects with the combination of ACE DD and CYP11B2 CC genotypes might have a better BP response to HCTZ than the other genotypic combinations of these 2 genes.

Adult ; Aged ; Aged, 80 and over ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide ; Sodium Chloride Symporter Inhibitors ; therapeutic use