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A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11 , NPM1 , RUNX1 , ASXL1 , TET2 , DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3 /ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.

Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1 , CEBPA , IDH2 , RUNX1 , WT1 , ASXL1 , DNMT3A and FLT3 , that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis ( P <0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

Hypermethylation of the distal CEBPA promoter region has been reported to result in the downregulation of CEBPA expression in several malignancies. However, the clinical implication of CEBPA hypermethylation in acute myeloid leukemia (AML) remains unclear. To investigate the correlation between CEBPA hypermethylation and clinical features in AML, quantitative MassARRAY analyses for CEBPA methylation status were performed on a cohort of 193 patients. High CEBPA methylation group ( CEBPA high-meth , n =28) and low methylation group ( CEBPA low-meth , n =165) were defined by using two-way hierarchical clustering. With a median follow-up of 48 months, among the 125 patients receiving standard induction therapy, CEBPA high-meth was associated with better treatment response (complete remission rate 93.3% versus 73.6%, P =0.116). In patients with normal karyotype and without CEBPA and NPM1 mutations, the CEBPA high-meth had longer overall survival (OS) than the CEBPA low-meth ( P =0.028). Multivariate analysis further supported that the CEBPA methylation was an independent prognostic factor for disease free-survival (hazard ratio=0.416; 95% confidence interval, 0.223–0.777, P =0.006) and OS (hazard ratio=0.406; 95% confidence interval, 0.166–0.996, P =0.050). We conclude that CEBPA methylation status is a useful prognostic biomarker for AML patients.

The functions of microRNAs (miRNA/miR) in the development of cervical cancer remain largely undefined. The present study investigated the role of miR-195 in cervical cancer development. The expression of miR-195 mimics in the cervical cancer HeLa cell line significantly decreased the cell proliferation, migration and invasion capacities in vitro. Using miRNA target prediction algorithms and reporter assays, cyclin D2 (CCND2) and v-myb avian myeloblastosis viral oncogene homolog (MYB) were identified as direct targets of miR-195. Moreover, miR-195 repressed the expression of CCND2 and MYB in the HeLa cells at the mRNA and protein levels. Finally, the expression of miR-195 was downregulated in cervical cancer tissues compared with normal tissues. Together, these data suggest that miR-195 is a tumor suppressor in cervical cancer.

Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98 – HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger ( P =0.0076) and female ( P =0.0111), with almost all having the M2-subtype of AML ( P <0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P =0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P =0.003). The NUP98–HOXA9 fusion was strongly associated with KRAS and WT1 mutations ( P =0.015 and P =0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/ HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98 – HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group.

As an important breakthrough to speed up the new-type urbanization, the characteristic towns are conducive to solving the problem of developing kinetic energy transformation in the current supply-side structural reform in China. Shanghai, as a global city, will create several distinctive towns with characteristics that highlighting local culture, which will contribute to the further improvement of regional development and the overall improvement of urban competitiveness. Based on the overall development in Shanghai, this paper fully evaluates the existing resource endowments and development status of Shanghai's existing characteristic towns through empirical research. Based on this, it sorts out the major bottlenecks and the goals and directions of the construction of characteristic towns from the perspective of \"people-oriented\", coordinating the residents' life, creative talents' work as well as tourists' travel. Finally, it gives specific direction and policy initiatives from the layout, characteristics, resource, industry, policy and other aspects to promote the construction of characteristic towns.