Objective To establish a paclitaxel-resistant BNX mouse model of human lung carcinoma, so as to provide evidences for studying chemoresistant mechanism and for screening of the reversal drugs in vivo. Methods The resistant model was produced by repeating a crossover subcutaneous injection of human lung cancer A549-Taxol cells and transplantation of tumor fragment into immune deficiency mice, so as to increase the tumor forming rate of A549-Taxol cells and shorten the tumor forming time. The expressions of GST-k, P-gpl70 and MMP-7 were examined by immunohistochemical staining. The chemosensitivities of tumor cells to Taxol were tested and IC50 was measured by MTT. Results Tumor niduses were observed subcutaneously in SCID mice 4 months after injection of A549-Taxol cells, and then the tumor fragment or the tumor cells suspension were injected to SCID mice again. After 3 times of crossover injection, the tumor cells grew faster and tumor niduses were formed 2 months after injection. The same procedure was done in BNX mice. Finally, we achieved a successful rate of 80% in tumor implantation in BNX mice; the tumor niduses could be formed in 3 weeks. P-gpl70, GST-* and MMP-7 expression was higher in the experiment group than that in the A549 control group. IC50 value of paclitaxel for A549-Taxol cells was 520 folds that of A549 cells. Conclusion We have successfully established paclitaxel-resistant lung carcinoma model in mice, which provides a new platform for further study on chemoresistant reversal strategy and individualized clinical treatment.

Objective To investigate the changes of iodide uptake and the expression of thyroidspecific genes in poorly differentiated follicular thyroid carcinoma (FTC) cells after transfection of human TSH receptor (hTSHR) gene in vitro. Methods The recombinant eukaryotic expression plasmid PcDNA3. 1/hTSHR-cDNA was transformed into DH5a bacterial for amplification and then the recombinant plasmid was extracted. The recombinant was identified with PCR amplifying, restriction enzyme digestion analysis and DNA sequencing. The recombinant plasmid pcDNA3.1/hTSHR was transfected into FTC-133 cell line by lipofectin methodin vitro. Immunofluorescence, iodide uptake studies and real time-PCR were applied to detect target protein expression. Statistical analysis was performed with t-test using SPSS 13. 0 software. Results Kpn Ⅰ and Xba Ⅰ restriction enzyme digestion, PCR amplifying and DNA sequencing confirmed that pcDNA3. 1/hTSHR was successfully constructed. After transfection of the recombinant plasmid pcDNA3. 1/hTSHR-cDNA and the stimulation of hTSH, the tumor cells displayed the expression of hTSHR protein at cell surface and cytoplasm. The iodine uptake in pcDNA3. 1/hTSHR transfected cells was 2. 9 times higher than that of control(pcDNA3.1(+) transfected cells) group(t = 28.63, P ＜0. 01). The expression of TSHR,NIS, TPO and Tg (mRNA levels) in pcDNA3. 1/hTSHR transfected cells were also significantly elevated by 1.74 (t =5.959, P＜0.01), 7.2 (t =3.807,P＜0.05), 2.88 (t=4.769,P＜0. 01) and 2.67 times (t=6.388,P ＜0.01) respectively compared to those of the control group. Conclusion The study demonstrates that iodide uptake may be reactivated by hTSHR receptor gene transfection in poorly differentiated FTC cell.

Objective To observe the molecular weight distribution of soybean peptides prepared by complex enzyme hydrolysation and tumor inhibitory effect in vivo or in vitro. Method The soybean protein was enzymolyzed to soybean peptides by Flavourzyme, Alealase and neutral protease, at(50-55)℃, followed by separation, absorption,affination, ultra centrifuge and spray drying. The soybean peptides were passed Sephadex G25 column at 0.5ml/min with 0.1mol/L Tris-HCl buffer. The fragment of fluid collected was determined by UV at 280nm and HPLC. Then the molecular weight distribution was calculated. The inhibitory effect on ansplant glioma (G422) at dose 1.25, 2.5 and 5g/kg bw (ig daily for 11 d) was tested in mice and in Hep-2 in vitro. Results The peptides contents in three batches were 54.6%, 51.9%, 51.8% respeclively. The molecular weight

OBJECTIVETo explore the role of -1C/T single nucleotide polymorphism within Annexin A5 gene in the genetic susceptibility to coal worker's pneumoconiosis (CWP).

METHODSFour hundred and seventy CWP Han chinese patients and 428 Han chinese controls were enclosed in present case-control study. All subjects were exposed to coal dusts. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1C/T SNP in Annexin A5 gene for all subjects. The relationship between the -1C/T SNP in Annexin A5 gene and CWP was analyzed.

RESULTSCT/TT genotype in -1C/T SNP was associated with a significantly decreased risk of CWP, as compared with the CC genotype among subgroups exposed to coal dusts for ≥ 27 years (adjusted OR = 0.65, 95%CI: 0.44 - 0.98, P = 0.039) and patients with CWP at stage II (adjusted OR = 0.55, 95%CI: 0.34 - 0.90, P = 0.028).

CONCLUSIONThe results of present study suggest that the Annexin A5 -1C/T polymorphism may be involved in the development of CWP in Han Chinese coal miners.

Aged ; Annexin A5 ; genetics ; Anthracosis ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo explore the possible association between six single nucleotide polymorphisms (SNPs) of Fas pathway genes and the risks of coal worker pneumoconiosis (GWP).

METHODSThis case-control study consisted of 511 male patients with CWP and 530 male controls from the same coal mines. Five SNPs of Fas pathway genes were detected by restriction fragment length polymorphisms (PCR-RFLP) and CASP3 (rs6948) was genotyped by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTSThere were no differences of genotype frequencies of 6 SNPs between cases with CWP and controls. A significant increased risk of CWP was found in subjects with CASP8-652DD genotype as compared to subjects with CASP8-652II genotype (P < 0.05), and the further stratification analysis showed that smoking cases with CWP stage I, long exposure time and CASP8-652DD genotype had high risk of CWP (P < 0.05). The analysis of gene-gene interactions indicated that the carriers with FAS-1377GG/CASP8-652DD, FAS-670AG/CASP8-652DD and FASL-844CT/CASP8-652DD had the increased risk of CWP, and the carriers with FAS-1377GA/CASP8-652ID had the reduced risk of CWP. There were no significant differences of exposure times among the cases with CWP stage I and 3 genotypes of CASP8-652.

CONCLUSIONCASP8-652 6N DD genotype may play a role in CWP development and interact with SNPs of FAS-1377, FAS-670 and FASL-844.

Aged ; Aged, 80 and over ; Anthracosis ; genetics ; Case-Control Studies ; Caspase 8 ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; Signal Transduction ; fas Receptor ; genetics

OBJECTIVEAnalyzed associations among the incidence of coal workers' pneumoconiosis from 2003 to 2008, jobs, exposure years and cumulative total dust exposure levels (CTE) and found the current characteristics of the mine incidence of pneumoconiosis disease.

METHODScollected the health care information of the new diagnosed pneumoconiosis of underground mine workers from 2003 to 2008 and the dust monitoring data of underground mine from 1949 and estimated the personnel cumulative total dust exposure levels (CTE); analyzed the incidence features of the new diagnosed pneumoconiosis.

RESULTSThe rates of health surveillance of workers were gradually improved from 2003 to 2008 and 296 new coal workers pneumoconiosis were diagnosed. The total incidence was 0.57%, and the average annual rate was 0.32%. Among the new diagnosed cases, phase I accounted for 90.5% and the 87.2% from coal mine drillers. The shortest exposure period was 3 years and the longest was 38 years, and the cumulative total dose of dust was varied between 86.1 and 4926 mg/m(3) per year. The total dust accumulated limited dose was calculated by the percentile method to prevent 99% of miners from pneumoconiosis, which was 120.6 mg/m(3) per year, so we suggested that the exposure years should be shorter than 13 years under the current working conditions.

CONCLUSIONSPreventive coal workers' pneumoconiosis should be focused on mine drillers and their limited exposure years should be within 13 years.

Anthracosis ; China ; epidemiology ; Coal Mining ; Dust ; analysis ; Humans ; Incidence ; Middle Aged ; Pneumoconiosis ; epidemiology

Objective To compare the efficacy and safety of gefitinib, erlotinib, and afatinib in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods PubMed, EMBASE, and The Cochrane Library were searched to identify the relevant literatures published from December 2008 to December 2018. Bayesian network meta-analysis was carried out to rank the three treatments. Results A total of ten eligible studies involving 2275 patients were enrolled. In terms of efficacy, the surface under the cumulative ranking (SUCRA) indicated that erlotinib performed best in progression-free survival(PFS)(0.88), afatinib performed best in objective response rate(ORR)(0.82) and disease control rate(DCR) (0.86), gefitinib performed worst in PFS (0.45), ORR(0.42), and DCR(0.45). For safety, the differences of grade 3 or 4 adverse events rate (OR=0.29,95%CI:0.08-0.98) and discontinuation rate(OR=0.14,95%CI:0.01-0.8) between erlotinib and the platinum-based doublet chemotherapy were statistically significant. The ranking results also supported that erlotinib was the safest. SUCRA results suggested that gefitinib (0.31) had a lower grade 3 or 4 adverse events rate than afatinib (0.57), and the possibility of discontinuation in gefitinib (0.44) was similar to that of afatinib (0.41). Conclusion Erlotinib might be the preferred first-line treatment for advanced NSCLC after weighing and balancing the benefits and risks.

BACKGROUNDThe prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma.

METHODSProteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test.

RESULTSSixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01).

CONCLUSIONSDifferentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.

Adolescent ; Adult ; Aged ; Cytoskeletal Proteins ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Female ; Glutathione S-Transferase pi ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Proteome ; metabolism ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Thymoma ; classification ; metabolism ; Tissue Array Analysis ; Young Adult

Objective To develop the National Norms of Negligence (NNN) for rural children aged 0 to 35 months.Methods According to multi-stage stratified cluster sampling principle,10 provinces or municipalities (Jilin,Shaanxi,Shanxi,Beijing,Anhui,Jiangsu,Hunan,Hubei,Yunnan,Chongqing) in China were selected.A national research group was formed collaboratively.A questionnaire was designed by ourselves.According to several statistical analysis methods,such as item,factor and reliability analysis etc.we determined the norm.The evaluation criteria of the scale were determined by percentile method.Finally,the reliability and validity of the norm were evaluated.Results In total,2310 children were surveyed,in which the effective sample were 2227,with an effective rate as 96.4％.The scale consisted of 6 neglected dimensions and 65 items in total.The total Cronbach's α coefficient of the scale was 0.903,with the split-half reliability coefficient as 0.829,the parallel reliability as 0.720 and the re-test reliability as 0.678,respectively.The total neglect cut-off score of this scale was 139.Conclusion The scale seemed to have perfect stability and reliability and all the statistical indicators met the psychometric demands.

OBJECTIVETo analyze the clinical characteristics of hospitalized pediatric patients infected with 2009 H1N1 influenza.

METHODSTotally 159 children (83 male and 76 female) with influenza A (H1N1) confirmed by the real-time reverse-transcriptase-polymerase-chain-reaction assay were admitted to a special ward of Capital Institute of Pediatrics from November 2009 to January 2010. Clinical manifestations, laboratory and therapy data from the hospitalized children were collected by designed case report form and analyzed.

RESULTSOut of 159 hospitalized patients, 139 (87.4%) were under the age of 5 years and 34.0% of them had at least one underlying medical conditions. Proportions of the severe cases, pneumonia and underlying medical diseases were similar between the 78 infants and 81 older children. All of these 159 cases had influenza-like symptoms at onset and the most common presentations were fever (115 cases, 72.3%) and cough (154 cases, 96.8%). Five severe cases presented dyspnea, cyanosis and hypoxemia. The virus easily invaded into the lower respiratory tract as indicated by that 61% of the cases had findings consistent with pneumonia by X-ray and/or CT and 21.6% had bacterial co-infection. Part of them had mycoplasma pneumonia (20 cases, 27.0%) or other respiratory viruses (5 cases, 3.1%) co-infection simultaneously. The duration of fever was similar between the H1N1 virus sole infection group and the co-infection group (t = 0.975, P > 0.05), but the average course of the disease and hospitalized days of the latter group were longer than the former (t = 3.182 and 3.190, P < 0.01). The proportion of children with pneumonia in the co-infection group was significantly higher than that in the H1N1 sole-infection group (χ(2) = 4.082, P < 0.05).

CONCLUSIONSMost of the H1N1 infected pediatric patients had mild respiratory symptoms, a few of them developed severe manifestations. Dyspnea and hypoxemia were the early signals for the developing severe cases. Rational and experienced treatment with antibiotics was important addition to the antiviral therapy for those co-infected with bacteria.

Child ; Child, Hospitalized ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; diagnosis ; epidemiology ; pathology ; therapy ; Male