Background The infection rate of human papillomavirus (HPV) is high in the coastal regions of China. However, the infection rate among high-risk genotypes of women in Putian City is unknown. Therefore, this study aimed to analyse the epidemiology of high-risk HPV infection among women in Putian and provide a reference for the diagnosis, treatment and vaccination of cervical cancer in this region. Methods The data used were obtained from the Chinese government’s public health program (“Cervical and Breast Cancer Screening Project”). A total of 40,693 female cervical cell exfoliation samples screened for high-risk HPV at the Affiliated Hospital of Putian University from July 2020 to December 2021 were enrolled. DNA was extracted using a fully automatic extractor. Then, 14 high-risk genotypes of HPV were detected by polymerase chain reaction. The characteristics of HPV infection, distribution of high-risk genotypes, infection types and thinprep cytologic test (TCT) classification at different age groups were analysed. Results Among the 40,693 samples, 3899 were infected with HPV, with an infection rate of 9.6%. Accordingly, HPV infection rates gradually increased with age, and statistically significant differences were observed among age groups (χ2 = 74.03, P < 0.01). The infection rates of high-risk HPV52, HPV58 and HPV16 were in the top three and increased with age. Single infection was dominant (84.7%), followed by double infections (12.7%). The cervical cytology of 3899 HPV-positive people can be classified into negative for intraepithelial lesion and malignancy (NILM, 88.0%), atypical squamous cells of undetermined significance (ASC-US, 6.6%), atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H, 1.4%), low-grade squamous intraepithelial lesion (LSIL, 3.2%) and high-grade squamous intraepithelial lesion (HSIL, 0.8%). HPV16 infection rate increased with increasing severity of cervical cytology (χ2trend = 43.64, P < 0.01), whereas the infection rates of HPV52 (χ2trend = 13.89, P < 0.01) and HPV58 (χ2trend = 13.50, P < 0.01) showed opposite trends. Conclusion The infection rate of female HPV high-risk screening in this region was 9.6% and mainly involved single infections. In addition, HPV16, HPV52 and HPV58 were closely related to the severity of cervical cytology. Effective screening, vaccination and education are needed. The 9-valent vaccine will be effective in reducing cervical pre-invasive disease. It would also be reasonable to state that the rising trend in HPV infection and high grade cytology with age emphasises the need to target older women with screening. Vaccination of younger women (aged ≤ 25) will lay the foundation for better cancer outcomes in the future.
Background: The D816V mutation of c-KIT can constitutively activate tyrosine kinase, thereby promote core binding factor acute myeloid leukemia (CBF-AML) cell proliferation and inhibit apoptosis. Previous studies have indicated similar proliferation and apoptosis between N822K and D816V mutations.The current study aims to determine the occurrence and potential functions of N822K mutation-induced c-KIT activation in AML cells, and explore possible mechanisms of poor prognosis of CBF-AML. Methods: c-KIT N822K mutation status in AML cells was determined by exon 17 sequencing. The level of c-KIT expression was detected by flow cytometry (FCM) and colony formation was assessed after hu-SCF stimulation. After exposure to sunitinib (a kind of tyrosine kinase inhibitor, TKI), cell proliferation inhibition was tested by MTT, cell cycle and apoptosis were measured by FCM, autophagy was assessed by fluorescence microscopy and immunoblotting. Results: Kasumi-1 cell line was detected to bear c-KIT N822K (T>A) mutation. After hu-SCF stimulation, CD117 expression was decreased and the colony formation efficiency was not altered in Kasumi-1 cells. After sunitinib inhibited the c-KIT activity, the colony formation efficiency was reduced, and the half-maximal inhibitory concentration (IC 50 ) of sunitinib was low (0.44±0.17μM) at 48 hours. Moreover, cells were arrested in G0/G1 phase, corresponding to an increase of apoptosis ratio. Acidic vesicular organelles (AVO) were observed along with an altered expression of autophagy-related proteins in Kasumi-1 cells. Conclusions: Our data indicated that inhibition of N822K T>A mutation-induced constitutive c-KIT activation in AML cells triggered apoptotic and autophagic pathways leading to death, and c-KIT N822K mutation may have clinical application as a CBF-AML treatment target.
Background: Chromosomal translocations of the mixed-lineage leukemia gene (MLL; tMLL) correlate with resistance to therapy and an extremely poor prognosis for individuals with Acute Myeloid Leukemia (AML). The underlying mechanisms are still unknown. This study aims to identify the key genes and the potential molecular mechanisms involved in MLL rearrangement in AML using a bioinformatics approach. Methods:The gene expression profiles from 15 individuals with partial tandem duplication of the MLL gene (MLL-PTD)-AML and 10 tMLL-AML samples were downloaded from the Gene Expression Omnibus (GEO) database. The Differentially Expressed Genes (DEGs) were selected and functional enrichment analyses were performed. The Protein-Protein Interaction (PPI) network was established and visualized in Cytoscape. The hub genes were identified by CytoHubba and significant modules were screened out by Molecular Complex Detection (MCODE). Results:We categorized a total of 885 DEGs comprising 330 upregulated and 555 downregulated genes. The majority of DEGs were significantly enriched for calcium ion transmembrane transport, embryonic skeletal system morphogenesis and cell proliferation processes. Several pathways were enriched, including those associated with PI3K-Akt signaling and insulin resistance. We identified 32 hub genes and screened out 2 modules. Conclusion:The genes we have identified in this study may represent potential biomarkers for MLL-rearranged AML and contribute to the development of novel therapeutic strategies.
Sitcoms production teams often choose actors with unique styles. Longevity of actors' performance and versatility are two major qualities that the sitcom actor should maintain [2]. Old actors are experienced, while the new actors can bring up the spirit of contemporary society. Therefore, both kinds of actors are required for sitcoms. Different departments in the production team all support actors to deliver the purpose of the sitcom to the audience. Directors help to form the character and select suitable actors under auditions and feelings. Cinematographer Cameraman uses the Three Lens Model and the dolly shot to exaggerate the detail performance of the actors with the demonstration of I love Lucy and the Big Bang theory. Costume and makeup help to deliver the historical background and better the looking of characters in the screen with examples from happy days. The use of Laff Box brings tremendous benefits for the sitcoms. The relationships between actors and audience are gradually closer as the century and technology developed, this can be seen from the Chinese sitcom apartment. Other sitcoms such as growing pains, friends and the Hank McCune show are useful to clarify the findings and ideas in this paper as well. The findings can be used for the director to make a successful sitcom with suitable actors.
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