Association between PD-L1 and HPV status and the prognostic value for HPV treatment in premalignant cervical lesion patients.

The difference of PD-L1 expression between only HPV-positive patients and premalignant cervical lesion patients did not be reported in present studies. And to test the PD-L1 expression in some cervical cell lesion studies using cervical exfoliated cells sample also was ignored. Meanwhile, the PD-L1 expression as a predictive biomarker still existed controversy. So in the study, first to compare the expression of PD-L1 between only HPV-positive patients and premalignant cervical lesion patients, then to research the association between PD-L1 and HPV status, lastly to explore the possible prognostic value for HPV treatment in premalignant cervical lesion patients.Cervical exfoliated cells samples of 54 premalignant cervical lesion patients with HPV16 infection were collected; meanwhile the cervical exfoliated cells samples from 20 healthy women without HPV infection and 20 patients with only HPV16 infection but cervical cytology normal were collected as 2 control groups. Flow-through hybridization and gene chip (FHGC) was used to detect the HPV type, the PD-L1 expression was tested by Flow cytometry analysis, the methylation-sensitive high-resolution melting (MS-HRM) was used to test the HPV16 L1 gene methylation. The 54 premalignant cervical lesion patients were followed up in 18 months to assess the prognostic value of PD-L1 for HPV treatment.The PD-L1 positive cell rate and mean fluorescence intensity of PD-L1 positive cell in premalignant cervical lesion patients with HPV16 infection were higher than 2 control groups. Mean fluorescence intensity of PD-L1 positive cell were increased in 54 cases when existing multiple HPV status and high HPV16-L1 gene methylation (L1 gene methylation more than 50%). High PD-L1 expression (PD-L1 positive cell rate more than 10%), high HPV16-L1 gene methylation, and multiple HPV infection status could prolong the time to clean HPV infection by Kaplan-Meier analysis. Multivariate Cox proportional hazards analysis also showed that all of high PD-L1 expression, high HPV-L1 methylation, and multiple HPV infection status should increase the risk of HPV unclearance in premalignant cervical lesion patients; the hazard ratio (HR) was 2.043 (CI: 1.050-3.973), 2.797 (CI: 1.277-6.122), and 3.050 (CI: 1.406-6.615).PD-L1 expression only was correction with HPV infection when the infection induced the cervical cells to create the lesion. PD-L1 was the risk factor of HPV unclearance in premalignant cervical lesion patients, so anti-PD-L1 therapy could be a potential effectiveness way of HPV infection in premalignant cervical lesion patients.

Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China.

Human papillomavirus (HPV) L1 gene methylation deeply involved in the progression and heterogeneity of cervical cell epithelial lesions. The DNA ploidy also represented the early lesions of cervical cell, and it was associated with different HPV infection status in different ethnic women. So, the research was to explore whether it was possible that HPV L1 gene methylation and HPV infection status as the risk factors to lead to the differences of cervical epithelial cells' lesions in different ethnics women.The flow-through hybridization and gene chip for HPV genotypes test, general characteristics, and cervical exfoliated cell samples were collected from 94 Uygur and 79 Han women with HPV-16 infection. The cases were divided into the single HPV-16 (sHPV-16) infection group and multiple HPV-16 (mHPV-16) infection group in each ethnic women. The DNA ploidy was analyzed by flow cytometry, and the methylation-sensitive high resolution melting (MS-HRM) was used to test the HPV-16 L1 gene methylation, the results of methylation was segmented into mild methylation, moderate methylation, and severe methylation groups. Multifactor logistic analysis explored the relation between DNA heteroploid and HPV-16 infection status, HPV-16 L1 gene methylation in different ethnic women.The higher proportion of mHPV-16 infection in Uygur than Han women (61.7% vs 38.0%). L1 gene methylation had statistic difference between single and mHPV-16 infection under the same ethnic women. The proportion of DNA heteroploid had statistic difference between different HPV-16 infection status or different L1 gene methylation grades in Han or Uygur women. Both L1 gene methylation and HPV infection status were the risk factors of DNA heteroploid. Compared to the sHPV-16 infection, the odds ratio (OR) of mHPV-16 infection were 4.409 (CI: 1.398-13.910) and 3.279 (CI: 1.069-10.060) in Han and Uygur women. Compared the mild L1 gene methylation, the OR of moderate L1 gene methylation were 3.313 (CI: 1.002-10.952) and 5.075 (CI: 1.385-18.603) in Han and Uygur women, the OR of severe L1 gene methylation were 20.592 (CI: 3.691-114.880) and 63.634 (CI: 10.400-389.368) in Han and Uygur women.The study first reported that HPV L1 gene methylation and HPV infection status were the risk factors to the DNA heteroploid of cervical cell in different ethnics women, HPV L1 gene methylation and infection status should be recommended to the existing system of cervical lesion screening in order to provide better serves for the HPV infected women, especially for the ethnic women with high proportion of severe L1 gene methylation and multiple infection status.

Antioxidant effects of the Uygur herb, Foeniculum Vulgare Mill, in a rat model of hepatic fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate therapeutic and antioxidant effects of Uygur Herb Foeniculum Vulgare Mill (FVM) in hepatic fibrosis rats.</p><p><b>METHOD</b>Hepatic fibrosis model was built in rats by subcutaneous injection with 40% CCl4 olive oil mixture. At the same time the rats were given high lipoid-low protein animal feeds for 5 weeks. 94 male SD rats were randomly divided into six groups :blank control group (A-group), 8 rats were feed in normal; prevention model control group (B-group), 10 rats were given saline solution by intragastric administration during make of hepatic fibrosis model; FVM prevention group (C-group), 10 rats were given FVM by intragastric administration during make of hepatic fibrosis model; model control group (D-group), FVM treatment group (E-group); Fuzhenghuayu treatment group (F-group). 22 rats in each D, E, F-group were respectively given saline solution, FVM and Fuzhenghuayu by intragastric administration after hepatic fibrosis model were built. At the 5-th weekend, A, B, C- group rats were sacrificed. At the 6-th, 7-th, 8-th, 9-th weekend, 4-6 rats in D, E, F-group were sacrificed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) and 8 - hydroxy-2-deoxyguanosine (8-OHdG) were detected, liver tissue homogenate superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) were detected. Histopathologic changes were observed after H.E and Masson staining. The expression of alpha-smooth muscle actin(a-SMA) were detected by immunohistochemical staining. The data were analyzed by SPSS17.0 software.</p><p><b>RESULTS</b>The serum levels of ALT, AST, HA, and LN in the FVM prevention group were significantly reduced compared to the prevention model control group.(P less than 0.05). Rats in FVM treatment group appeared a marked lower serum levels of ALT, AST, HA compared to the model control group (P less than 0.05), and a distinguished lower Inflammation grade and fibrosis stage (P less than 0.05) when the liver section were assayed as well; Rats in FVM treatment group and FVM prevention group had a conspicuous lower content of MDA, 8-OHdG, fibre and a-SMA expression (P less than 0.05), a significantly higher level of SOD, GSH-Px compared to those of in the model control groups.</p><p><b>CONCLUSIONS</b>Foeniculum Vulgare Mill declines liver inflammation response ,and prevent the hepatic fibrosis progression,, this may be due to its effects of antioxidative results.</p>

[Expression of CD4+ CD25+ regulatory T cells and TGF-ß1 in patient with idiopathic thrombocytopenic purpura].

AIM: To investigate the expression rate of CD4+ CD25+ regulatory T cells and TGF-ß1 in peripheral blood of the patients with idiopathic thrombocytopenic purpura (ITP), and the role they play in the pathogenesis of ITP. METHOD: The population of CD4+ CD25+ regulatory T cells in peripheral blood of 31 patients and 25 healthy donors was evaluated by flow cytometry, ELISA was used to test the level of TGF-ß1 in blood serum, and analysed the correlation between levels of CD4+ CD25+ regulatory T cells and TGF-ß1. RESULTS: ITP patients had a lower proportion of CD4+ CD25+ regulatory T cells than the healthy donors (P<0.05). The level of TGF-ß1 in ITP patients was also lower than healthy donors (P<0.05). There was not positive correlation between levels of CD4+ CD25+ regulatory T cells and TGF-ß1 (P<0.05). CONCLUSION: The results indicate that the decreasing of CD4+ CD25+ regulatory T cells in ITP patients may be connected with cellular immunity disturbance of idiopathic thrombocytopenic purpura. Further research need to be performed in metabolic changes on CD4+ CD25+ regulatory T cells and TGF-ß1 in patients with idiopathic thrombocytopenic purpura.