Analysis on Factors Related to Rabies Epidemic in China from 2007-2011

To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemiological methods and statistical analysis was used on data collected from the National Disease Reporting Information System between 2007 to 2011 and the National Active Surveillance System between 2007 and 2010. Our analysis shows that while the number of human rabies cases decreased year by year, the number of districts reporting cases did not show significant change. The situations in Guangdong, Guangxi, Guizhou and Hunan provinces clearly improved over the period but they remain provinces with high-incidence, and consequently influence the epidemic situation of surrounding provinces and possibly the whole country. Summer and autumn were high-incidence seasons. Farmers, students and pre-school children represent the high-risk populations, and rates of cases in farmers increased, those for students decreased, and pre-school children remained unchanged. Provinces with active surveillance programs reported a total of 2346 individual cases, of which 88.53% were associated with canines. Postexposure prophylaxis （PEP） of rabies cases was not significantly improved, whereas PEP in post-exposure population was good. In rural regions of China, canine density was reduced somewhat, and the immunization rate increased slightly. Finally we show that while the epidemic decreased 2007 to 2011 in China, cases continued to be diffused in certain regions. Lack of standardization of PEP on rabies eases was the main reason of morbidity. The high density and low immunization of dog in rural areas and the defective situation of PEP are still continuous occurrences in China and remain a cause for concern.

EGFR Gene Mutation and Methodological Evaluation in 399 Patients with Non-small Cell Lung Cancer

The purpose of the present study was to study the characteristics of epidemic growth factor receptor(EGFR)gene distribution in patients with non-small cell lung cancer(NSCLC),and to detect the mutation rate of EGFR gene by Sanger sequencing and amplification refractory mutation system(ARMS)-PCR.Paraffin-embedded sections of NSCLC tissues from 399 NSCLC patients diagnosed in Renmin Hospital of Wuhan University were collected,103 of them were detected for exons 18-21 mutation of EGFR by Sanger sequencing method,296 cases were detected for exons 18-21 mutation by ARMS-PCR method.DNA extraction of both groups was performed with Qiagen QLAamp DNA FFPE Tissue KIT.Comparisons of detection rates between the two methods were conducted by row X list chi-square test.The total mutation rate of EGFR gene detected by Sanger sequencing was 21.4%,exons 18-21 and combined mutation rates were 1.0%,9.7%,1.0%,7.8%and 2.0%,respectively.And the proportions were 4.7%,45.2%,4.7%,36.3%and 9.4%respectively.The total mutation rate detected by ARMS-PCR was 51.4%,exons 18-21 and combined mutation rates were 2.7%,27%,1.7%,18.2%and 1.7%,respectively.The proportions were 5.3%,52.6%,3.3%,35.5%and 3.3%respectively.Further analysis of mutation rate showed that there was significant difference between the two methods in detecting total mutation of EGFR gene(P<0.001).There were significant differences in mutation detection rates of exons 19 and 21(P<0.001,P<0.05),but there were no significant differences in other exons.And there was no significant difference in mutation detection rates between the two methods.The mutation rate of EGFR gene in NSCLC patients was 50%.And exon 19 deletion was the most common mutation type,followed by exon 21 mutation.Compared with Sanger sequencing method,ARMS method is more sensitive with significant advantages in detecting exon 19 deletions and exon 21 mutations,which can be widely used in clinical detection of EGFR gene mutations.The results of this study will further guide patients with advanced NSCLC to select TKI targeted drugs,and provide clinical diagnostic basis for targeted therapy of NSCLC patients.

ANTIPROLIFERATIVE ACTIVITY OF HUMAN IFN-γ-EGF_3 FUSION PROTEIN ARE RELATED TO ITS EGF RECEPTOR COMPETITION

The relationship between antiproliferative effect of human IFN γ EGF 3 fusion protein and the influence of EGF receptor binding activity has been studied on A431 cell line. Antiproliferative activity of human IFN γ EGF 3 was higher than that of its parent IFN γ. In the 125 I EGF receptor competition experiment, the inhibition of EGF receptor binding capacity on the target cells was observed in the treatments of human IFN γ or IFN γ EGF 3, but the later was more significant. Our data suggests that the antiproliferative effects by IFN γ and its fusion protein are closely related to their EGF receptor competitions.

Design, Synthesis and Biological Activities of N-（Furan-2-ylmethyl）-lH-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents

A series ofN-（furan-2-ylmethyl）-lH-indole-3-carboxamide derivatives（6a--6p） was designed and synthe- sized for developing novel indole scaffolds as anticancer agents targeting the epidemal growth factor receptor （EGFR）, and the cytotoxic activities of the target compounds were evaluated against three EGFR high-expressed cancer cell lines[human lung adenocarcinoma cell line（A549）, Henrietta Lacks strain of cancer cell line（HeLa） and human colorectal cancer cell line（SW480）], one EGFR low-expressed cell line（human liver cancer cell line, HepG2） and one human liver normal cell line（HL7702） using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay, Some target compounds exhibited potent anficancer activities against A549, HeLa, SW480 and weak activities on HepG2, which signifies that the target compounds are likely to be EGFR inhibitors as expected. And they showed weak cytotoxic effects on HL7702, which implies the target compounds are probably to be of low toxicity against normal cells. Among them, the target compound 1-ethyl-N-（fttran-2-ylmethyl）-5-{2-{ [2-（2-methoxy- phenoxy）ethyl]amino}-2-oxoethoxy}-2-methyl-1H-indole-3-carboxamide（6p） with 2-{[2-（2-methoxyphenoxy）ethyl]- amino}-2-oxoethoxy group at the C5 position of the N-（furan-2-ylmethyl）-lH-indole-3-carboxamide scaffold exhibited the most potent anticancer activity. Also the binding interaction of the target compound 6p with EGFR was explored by molecular docking. Conclusively, the novel indole scaffold may be beneficial to investigate new anticancer agents for targeting the EGFR.