BackgroundCurrently, the role of human papillomavirus (HPV)-58 in southwestern China has been unexplored. Although there is some controversy, it is proposed that the viral load of HPV correlates with the severity of intraepithelial lesions.MethodsWe identified 7747 patients from south Sichuan and adjacent regions who were diagnosed with HPV between 2013 and 2017. The HR-HPV subtype distribution was analyzed and the patient’s viral loads were quantified using real-time RT-PCR.ResultsAmong all 7747 patients screened for HPV genotypes, 1728 patients (22.31%) were identified as having HR-HPV subtypes. In patients without intraepithelial lesions (12.41%), HPV-52, HPV-16, and HPV-58 were the three most prevalent HR-HPV subtypes. Moreover, HPV-16, HPV-58, and HPV-33 were the most prevalent subtypes in patients with cervical intraepithelial neoplasia grade II (CINII) (42.86%) and grade III (CINIII) (59.81%), and accounted for the majority of invasive cervical cancer (ICC) (69.34%). Thus, viral loads of HPV-58, HPV-16, and HPV-33 positively correlated with the severity of cervical lesions (P < 0.001, P = 0.016, P = 0.026, respectively). Using receiver operating characteristic (ROC) curve analysis, the optimum thresholds for predicting severe intraepithelial lesions of cases (CINI, CINIII and ICC) with HPV-16, HPV-58, and HPV-33, respectively, were obtained, which were 1, 0.93, and 0.25, respectively.ConclusionIn our study, we showed that HPV-16 was the most common carcinogenic HPV subtype in southwestern China followed by HPV-58 and HPV-33. Viral loads of these subtypes are associated with the severity of premalignant lesions in the cervix.Electronic supplementary materialThe online version of this article (10.1186/s12985-018-1003-x) contains supplementary material, which is available to authorized users.
Breast cancer is the most common malignant tumor in China and even in the world. DNA repair genes can lead to tumor metastasis by affecting cancer cell resistance. Studies have preliminarily shown that DNA repair genes are related to breast cancer metastasis, but it is not clear whether they can be used as a prediction of the risk of breast cancer metastasis. Therefore, this study mainly discusses the predictive value of DNA repair genes in postoperative metastasis of breast cancer. The nested case–control method was used in patients with breast cancer metastasis after surgery (n = 103) and patients without metastasis after surgery (n = 103). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. In protein expression, PARP1 (OR 1.147, 95% CI 1.067 ~ 1.233, P < 0.05), XRCC4 (OR 1.088, 95% CI 1.015 ~ 1.166, P < 0.05), XRCC1 (OR 1.114, 95% CI 1.021 ~ 1.215, P < 0.05), ERCC1 (OR 1.068, 95% CI 1.000 ~ 1.141, P < 0.10) were risk factors for postoperative metastasis of breast cancer. In addition, we used the ROC curve to study the optimal critical values of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA combined with the Youden index, and the effects of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA on breast cancer metastasis were verified again. Among them, the risk of metastasis in the PARP1 high expression group was 3.286 times that of the low expression group (OR 3.286, 95% CI 2.013 ~ 5.364, P < 0.05). The risk of metastasis in the XRCC4 high expression group was 1.779 times that of the low expression group (OR 1.779, 95% CI 1.071 ~ 2.954, P < 0.05). The risk of metastasis in patients with ERCC1 high expression group was 2.012 times that of the low expression group (OR 2.012, 95% CI 1.056 ~ 3.836, P < 0.05). So we can conclude that protein expression of PARP1 (cut-off value = 6, Se = 76.70%, Sp = 79.61%), XRCC4 (cut-off value = 6, Se = 78.64%0, Se = 79.61%), ERCC1 (cut-off value = 3, Se = 89.32%, Sp = 50.49%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of metastasis will increases. Due to PARP1, XRCC4 and ERCC1 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-XRCC4 = 0.343; rPAPR1-ERCC1 = 0.335; rXRCC4-ERCC1 = 0.388). The combined diagnosis of the PARR1, XRCC4 and ERCC1 have greater predictive value for the risk of metastasis of breast cancer (Se = 94.17%, Sp = 75.73%; OR 11.739, 95% CI 2.858 ~ 40.220, P < 0.05). The postoperative metastasis of breast cancer could be effectively predicted when the immunohistochemical scores met PARP1 (IHC score) > 6, XRCC4 (IHC score) > 6 and ERCC1 (IHC score) > 3. In addition, the combined diagnosis of PARP1, XRCC4 and ERCC1 has great predictive value for the risk of breast cancer metastasis.
PEG-PCL-PEG (PECE) hydrogel for intracameral injection as a sustained delivery system can get a stable release of the medication and achieve an effective local concentration. The injectable PECE hydrogel is thermosensitive nano-material which is flowing sol at low temperature and can shift to nonflowing gel at body temperature. This study evaluated the intracameral injection of bevacizumab combined with a PECE hydrogel drug release system on postoperative scarring and bleb survival after experimental glaucoma filtration surgery. The best result was achieved in the bevacizumab loaded PECE hydrogels group, which presented the lowest IOP values after surgery. And the blebs were significantly more persistent in this group. Histology, Massion trichrome staining and immunohistochemistry further demonstrated that glaucoma filtration surgery in combination with bevacizumab loaded PECE hydrogel resulted in good bleb survival due to scar formation inhibition. In conclusions, this study demonstrated that bevacizumab-loaded PECE hydrogel for intracameral injection as a sustained delivery system provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.
Objectives: This study aimed to determine expressions of methyltransferase-like 3 (METTL3) and METTL14, two enzymes essential for mRNA methylation at the adenosine (m 6 A), in oral squamous cell carcinoma (OSCC) and to investigate in vitro aggressiveness of their aberrant expressions. Methods: METTL3 and METTL14 expressions in 50 OSCC and 11 normal oral tissues were examined by immunohistochemistry. METTL3 and METTL14 expressions and m 6 A amounts were determined in three OSCC cell lines, including HN5, HN6, and HN15. Cell proliferation, migration, and invasion were studied by BrdU, wound healing, and Transwell chamber assays, after silencing of METTL3, METTL14, or both by siRNA transfection. Results: Immunostaining of METTL3 and METTL14 was localized in cancer cell nuclei.The mean percentages of METTL3-and METTL14-positive cells were significantly increased in OSCC tissues (p < 0.001). The percentages of METTL3-and METTL14positive cells were correlated with the advanced pTNM stages (p < 0.05) and with the degrees of histopathological differentiation in OSCC (r = 0.564 and r = 0.316, respectively; p < 0.001). By the COX multivariate analysis, both overexpressed METTL3 and METTL14 were significantly associated with short overall survival (p < 0.05).Both METTL3 and METTL14 expressions and the m 6 A amounts were significantly increased in HN6 (p < 0.05). Silencing of METTL3 and METTL14 in HN6 significantly inhibited cell proliferation (p < 0.01), but it failed to mitigate cell migration or invasion.Conclusions: METTL3 and METTL14 are overexpressed in OSCC tissues and in the HN6 OSCC cell line that promotes cell proliferation. Overexpressed METTL3 or METTL14 is found to be an independent prognostic factor for short overall survival in patients with OSCC.
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