[Current status of clinical trials of HPV therapeutic vaccines].

Cervical cancer mainly caused by human papillomavirus (HPV) infection has become a public health issue, which seriously threatens women 's health. To prevent HPV infection, the currently used prophylactic vaccines mainly induce a humoral immune response in the host, thereby generating neutralizing antibodies. In contrast, the design goal of therapeutic HPV vaccines is to induce a cell-mediated immune response in the host, primarily driven by Th1 cells, aiming to clear existing viral infections and slow down or inhibit tumor progression. Currently, several therapeutic HPV vaccines based on different mechanisms and techniques have entered clinical trials. This review will summarize the progress of these clinical trials, providing reference for the research and development of therapeutic HPV vaccines.

Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA.

Apurinic/apyrimidinic endonuclease1 (APE1), which has the dual functions of DNA repair and redox regulation, is considered to be a promising potential target in cancer treatment. Microarray and qRT-PCR were used to confirm the change of miRNA followed by analysis with comprehensive bioinformatics-based analysis. Both microarray and qRT-PCR demonstrated that 13 microRNAs (miRNAs) were significantly changed (>2-fold) in APE1 knockdown HOS cells; seven of them (hsa-miR-451, hsa-miR-1290, hsa-miR-765, hsa-miR-483-5p, hsa-miR-513a-5p, hsa-miR-129-5p and hsa-miR-31) were up-regulated and the other six (hsa-miR-29b, hsa-miR-197, has-let-7b, hsa-miR-324-5p, hsa-let-7i and hsa-miR-484) were down-regulated. Furthermore, pathway analysis showed that these miRNAs and their target genes affected by the expression of APE1 were involved in pathways relating to developmental processes, regulation of cellular processes, cell signaling (such as TGF-ß, Wnt, MAPK and the p53 signaling pathway) and cancers. There are putative binding sites of NF-κB, p53, HIF-1α, AP-1, PEBP2, ATF, NF-Y, Pax-2,CREB and c-Myb in the promoters of several down regulated miRNAs, indicating that APE1 may regulate miRNAs via transcription factors. Our data suggest that our understanding of the biological functions of APE1 will inevitably expand due to the novel pathways that APE1 uses to regulate gene expression through miRNAs.

Association of eNOS gene polymorphisms with essential hypertension in the Han population in southwestern China.

Endothelial nitric oxide synthase (eNOS) plays an important role in maintaining blood pressure homeostasis and vascular integrity. Polymorphisms in the eNOS gene have been found to be associated with hypertension in different human populations, including Northern and Southern Chinese Han populations. To examine the relationship of three eNOS gene polymorphisms, T-786C (rs2070744), G894T (rs1799983), and G10T (rs7830), with hypertension in the Han population in southwestern China, we carried out a study of the genotypes of three SNPs in 510 hypertensive and 510 normotensive subjects from the Yunnan Province by using PCR-RFLP and sequencing. Our SNP analyses showed that the distribution of the T-786C polymorphism did not differ between patients and controls, and that G894T and G10T are significantly associated with hypertension in females, adjusted for covariates. Compared with the other haplotypes, haplotype H1 (TGG), carrying protective 10G and 894G alleles, significantly decreased the risk of increased essential hypertension in females, with an odds ratio of 0.68 (P = 10(-5)). These results suggest that the eNOS polymorphism is one of the factors contributing to the predisposition for essential hypertension in the Han population in southwestern China.

Sequencing-based analysis of the HLA-DPB1 polymorphism in Nu ethnic group of south-west China.

In the present study, DNA typing for HLA-DPB1 was performed using polymerase chain reaction-sequencing-based typing method in 72 randomly selected Nu ethnic individuals inhabiting the Yunnan province of south-west China. Among the 12 detected DPB1 alleles, the most frequent was DPB1*1301, with the percentage of 20.83%, followed by DPB1*0501 (19.44%), DPB1*040101 (16.67%) and DPB1*2801 (9.72%). The allele DPB1*1501 was found for the first time in the Chinese population. Neighbour-joining showed that the Nu ethnic minority belonged to East Asian cluster and was most closely related to Lisu, being consistent with the historical records. In addition, the results obtained in this study will also provide useful information on organ transplantation, forensic investigations and disease association studies.

Polymorphism of the DPB1 locus in Hani ethnic group of south-western China.

Polymorphism of HLA-DPB1 was revealed with a sequencing-based typing (SBT) method in 47 unrelated healthy individuals from Yunnan Hani ethnic minority. The alleles DPB1*5901 and DPB1*7001 were detected for the first time in Chinese populations. A dendrogram showed that the Hani ethnic group belongs to the southern group of Chinese.

HLA-DPB1 allelic frequency of the Lisu ethnic group in the Southwest China and evolutionary relationship of Lisu with other populations.

A sequencing-based typing of human leukocyte antigen-DPB1 (HLA-DPB1) gene was carried out in 37 unrelated healthy individuals from the Yunnan Lisu ethnic minority. A total of 12 DPB1 alleles, in which DPB1*1301 (33.3%), DPB1*0402 (16.6%), DPB1*040101 (13.8%), and DPB1*0501 (11.1%) were highly predominant, were found, and allele DPB1*200102 was found for the first time in a Chinese population. A dendrogram constructed by neighbor-joining method showed that the Lisu ethnic group belongs to East Asian cluster.

Improving generalization performance using double backpropagation.

In order to generalize from a training set to a test set, it is desirable that small changes in the input space of a pattern do not change the output components. This can be done by forcing this behavior as part of the training algorithm. This is done in double backpropagation by forming an energy function that is the sum of the normal energy term found in backpropagation and an additional term that is a function of the Jacobian. Significant improvement is shown with different architectures and different test sets, especially with architectures that had previously been shown to have very good performance when trained using backpropagation. It is shown that double backpropagation, as compared to backpropagation, creates weights that are smaller, thereby causing the output of the neurons to spend more time in the linear region.