High-risk Human Papillomavirus Infection in Putian, China: A Cross-sectional Analysis of 98085 Women.

OBJECTIVE: To assess high-risk human papillomavirus (hrHPV) infection among women undergoing cervical cancer screening in Putian for establishing an optimal cervical cancer screening mode and preventive vaccination strategy for HPV. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: The Affiliated Hospital of Putian University for cervical cancer screening period, from August 2020 to December 2022. METHODOLOGY: Cervical cell specimens were obtained using 'two cancer screening platforms'. qRT-PCR and flow-FISH were used for hrHPV typing. The pathological diagnostic test was performed for the hrHPV-positive samples. The results concerning the relationships between hrHPV infection at different age groups and pathological diagnosis were analysed retrospectively. RESULTS: A total of 98085 hrHPV preliminary screening results in the Putian region and 9036 hrHPV-positive samples were included. The infection rate of hrHPV for the three infection modes increased with age. The 41-50 age group is the highest incidence which the phase from cervical intraepithelial neoplasia to cervical cancer. The top three hrHPV subtypes were HPV52, HPV58, and HPV16. The positive rate of HPV16 was positively correlated with the progression of cervical intraepithelial neoplasia. CONCLUSION: Effective screening, vaccination, and education must be provided because HPV infections are district-specific and age-specific. HPV16 is correlated with cervical cancer progression. Pathological diagnosis and prevention of cervical cancer infected with HPV16 must be conducted. KEY WORDS: hrHPV, Cervical cancer, Pathological diagnosis.

Regional distribution of the MTHFR C677T polymorphism in Chinese females.

Objective: For analyzing the distribution characteristics of MTHFR C677T polymorphism in Chinese females in order to provide information for reducing birth defects and formulating public health policies to prevent congenital malformations. Methods: Literature search in the last 6 years on "MTHFR C677T," "polymorphism" and "methylene tetrahydrofolate reductase." The included literature provides the MTHFR C677T frequency in healthy females in the corresponding regions. The data were grouped by the national administrative region as a unit to obtain the distribution information of the MTHFR C677T and alleles in the female population in every province, municipality or autonomous region. This was done for analyzing the overall distribution of the MTHFR C677T allele and the geographical distribution of pregnancy complications. Results: A total of 126 studies were included, covering five autonomous areas, four municipalities directly under the Central Government, as well as 22 provinces (except Taiwan Province) in China. MTHFR C677T polymorphism data of 27 groups of Chinese Han women and 31 groups of other Chinese females were obtained, and the chi-square test revealed notable inter-group differences (p = 0.000). The TT genotype and T allele of MTHFR C677T accounted for 18.2% (4.7%-38.3%) and 40.3% (19.7%-61.4%) of the Chinese female population, respectively, with a significant north-south difference. Chinese females had a consistent frequency of the T allele with the geographical distribution of pregnancy complications such as recurrent abortion and preeclampsia. Conclusion: With a obvious geographical gradient, the MTHFR C677T polymorphism distribution in Chinese females is consistent with the geographical distribution of multiple pregnancy complications, and the risk assessment for it might be included in primary prevention for birth defects.

Optimization of GPC3-specific chimeric antigen receptor structure and its effect on killing hepatocellular carcinoma cells.

To investigate the effect of optimized GPC3-specific chimeric antigen receptor (GPC3-CAR) structure on killing hepatocellular carcinoma (HCC) cells. We constructed three lentiviral expression vectors with different CAR structures by genetic engineering and molecular cloning techniques. These three CAR structures shared the same intracellular signaling region consisting of 4-1BB and CD3ζ, but had different hinge and transmembrane regions. Specifically, GPC3-O4-CAR contained an optimized CD8α hinge region and a 4-1BB transmembrane domain; GPC3-CD8-CAR contained an optimized CD8α hinge region and a CD8α transmembrane domain; and GPC3-ori-CAR contained an original CD8α hinge region and a 4-1BB transmembrane domain. With similar transfection efficiency, it was observed by fluorescence microscopy that GPC3-O4-CAR expression on the surface of 293 T cells was much higher than those of the other two. Cytotoxicity experiments showed that T or NK cells with GPC3-O4-CAR structure were more lethal and could secrete more IFN-γ than the other two. In conclusion, GPC3-O4-CAR can be efficiently and stably expressed on the cell surface. Moreover, both the killing effect of transduced T and NK cells on GPC3-positive HCC cells and release of IFN-γ are increased.

cIAP2 via NF-κB signalling affects cell proliferation and invasion in hepatocellular carcinoma.

AIMS: To investigate the role of cIAP2 in the malignant biological behaviours of hepatocellular carcinoma (HCC) cells and determine its mechanism of action. MAIN METHODS: cIAP2 protein expression was detected via immunohistochemistry (IHC) in 102 HCC specimens and 43 paracancerous liver tissues, and its relationship with clinicopathological features and patient prognosis was analysed. Then, short interfering RNA (siRNA) technology was used to knock down cIAP2 expression in BEL7402 and HepG2 cells. Cell Counting Kit-8 (CCK8) and Transwell assays were used to determine cell proliferation and invasion after knockdown of cIAP2 expression. The relationship between cIAP2 and the NF-κB pathway was explored via western blotting (WB) and a dual luciferase reporter system. Finally, nude mouse models of liver cancer were established to detect the effect of cIAP2 on tumourigenicity and the proliferation activity of orthotopic HCC cells. KEY FINDINGS: cIAP2 expression was significantly increased in HCC tissues and was correlated with intravascular thrombosis in HCC. High cIAP2 expression was correlated with poor patient prognosis. cIAP2 knockdown significantly reduced the proliferation and invasion of BEL7402 and HepG2 cells and the activity of the NF-κB pathway. Animal experiments showed that cIAP2 knockdown reduced the tumourigenicity of HepG2 cells in the liver of nude mice and the proliferation activity of the orthotopic HCC cells. SIGNIFICANCE: cIAP2 plays an important role in HCC proliferation and invasion and may exert its effects via the NF-κB signalling pathway.