Effects of theophylline combined with inhaled corticosteroids on patients with moderate and severe asthma and changes of T lymphocyte subsets in peripheral blood.

Introduction: Asthma is a common respiratory disease. Theophylline combined with inhaled corticosteroids (ICS) is a promising therapy for asthma. This study explored the therapeutic effects of ICS combined with theophylline on moderate and severe asthma patients and T lymphocyte subsets (CD3+CD8+ T cells) in peripheral blood. Material and methods: A total of 202 moderate and severe asthma patients were selected, with 101 treated with theophylline combined with ICS and 101 treated with ICS alone as controls. Lung function [forced expiratory volume within 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)] were tested using a spirometer. Asthma symptom control was evaluated by asthma control tests (ACT). The life quality was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). The number and percentage of CD3+ T, CD3+CD4+ T and CD3+CD8+ T cells in peripheral blood mononuclear cells were assessed by flow cytometry. The correlation between CD3+CD8+ T cells and lung function and asthma control of patients after combination therapy was analyzed by Pearson correlation analysis. Results: Compared with moderate and severe patients treated with ICS alone, theophylline improved the efficacy of ICS. Theophylline combined with ICS decreased IL-4 and IL-6 levels, and CD3+ T and CD3+CD8+ T cell number and percentage. After combined treatment, CD3+ CD8+ T cells in peripheral blood of patients were positively correlated with lung function and negatively correlated with asthma control. Conclusions: The additional use of theophylline improved the efficacy of corticosteroids in asthma patient treatment and reduced inflammation level and CD3+ T and CD3+CD8+ T cell contents in peripheral blood.

Development and validation of nomograms to recurrence and survival in patients with early-stage cervical adenocarcinoma.

PURPOSE: Cervical adenocarcinoma is one of the most common types of cervical cancer and its incidence is increasing. The biological behavior and treatment outcomes of cervical adenocarcinoma (CA) differ from those of squamous cell carcinoma (SCC). We sought to develop a model to predict recurrence and cancer-specific survival (CSS) deaths in CA patients. METHODS: 131 patients were included in model development and internal validation, and patients from the SEER database (N = 1679) were used for external validation. Multivariable Cox proportional hazards regression analysis was used to select predictors of relapse-free survival (RFS) and CSS and to construct the model, which was presented as two nomograms. Internal validation of the nomograms was performed using the bootstrap resampling method. RESULTS: Age, FIGO (International Federation of Gynecology and Obstetrics) stage, size of the tumor, lymph metastasis and depth of invasion were identified as independent prognostic factors for RFS, while age, FIGO stage, size of the tumor and number of positive LNs were identified as independent prognostic factors for CSS. The nomogram of the recurrence model predicted 2- and 5-year RFS, with optimism adjusted c-statistic of 75.41% and 74.49%. Another nomogram predicted the 2- and 5-year CSS with an optimism-adjusted c-statistic of 83.22% and 83.31% after internal validation; and 68.6% and 71.33% after external validation. CONCLUSIONS: We developed and validated two effective nomograms based on static nomograms or online calculators that can help clinicians quantify the risk of relapse and death for patients with early-stage CA.

Application of EfficientNet-B0 and GRU-based deep learning on classifying the colposcopy diagnosis of precancerous cervical lesions.

BACKGROUND: Colposcopy is indispensable for the diagnosis of cervical lesions. However, its diagnosis accuracy for high-grade squamous intraepithelial lesion (HSIL) is at about 50%, and the accuracy is largely dependent on the skill and experience of colposcopists. The advancement in computational power made it possible for the application of artificial intelligence (AI) to clinical problems. Here, we explored the feasibility and accuracy of the application of AI on precancerous and cancerous cervical colposcopic image recognition and classification. METHODS: The images were collected from 6002 colposcopy examinations of normal control, low-grade squamous intraepithelial lesion (LSIL), and HSIL. For each patient, the original, Schiller test, and acetic-acid images were all collected. We built a new neural network classification model based on the hybrid algorithm. EfficientNet-b0 was used as the backbone network for the image feature extraction, and GRU(Gate Recurrent Unit)was applied for feature fusion of the three modes examinations (original, acetic acid, and Schiller test). RESULTS: The connected network classifier achieved an accuracy of 90.61% in distinguishing HSIL from normal and LSIL. Furthermore, the model was applied to "Trichotomy", which reached an accuracy of 91.18% in distinguishing the HSIL, LSIL and normal control at the same time. CONCLUSION: Our results revealed that as shown by the high accuracy of AI in the classification of colposcopic images, AI exhibited great potential to be an effective tool for the accurate diagnosis of cervical disease and for early therapeutic intervention in cervical precancer.

A novel necroptosis-related lncRNA based signature predicts prognosis and response to treatment in cervical cancer.

Background: Necroptosis has been demonstrated to play a crucial role in the prognosis prediction and assessment of treatment outcome in cancers, including cervical cancer. The purpose of this study was to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship with immune microenvironment and response to treatment in cervical cancer. Methods: Data from The Cancer Genome Atlas (TCGA) were collected to obtain synthetic data matrices. Necroptosis-related lncRNAs were identified by Pearson Correlation analysis. Univariate Cox and multivariate Cox regression analysis and Lasso regression were used to construct a necroptosis-related LncRNAs signature. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, receiver operating characteristic (ROC) curve, nomogram, and calibration curves analysis were performed to validate this signature. Gene set enrichment analyses (GSEA), immunoassays, and the half-maximal inhibitory concentration (IC50) were also analyzed. Results: Initially, 119 necroptosis-related lncRNAs were identified based on necroptosis-related genes and differentially expressed lncRNAs between normal and cervical cancer samples. Then, a prognostic risk signature consisting of five necroptosis-related lncRNAs (DDN-AS1, DLEU1, RGS5, RUSC1-AS1, TMPO-AS1) was established by Cox regression analysis, and LASSO regression techniques. Based on this signature, patients with cervical cancer were classified into a low- or high-risk group. Cox regression confirmed this signature as an independent prognostic predictor with an AUC value of 0.789 for predicting 1-year OS. A nomogram including signature, age, and TNM stage grade was then established, and showed an AUC of 0.82 for predicting 1-year OS. Moreover, GSEA analysis showed that immune-related pathways were enriched in the low-risk group; immunoassays showed that most immune cells, ESTIMAT scores and immune scores were negatively correlated with risk score and that the expression of immune checkpoint-proteins (CD27, CD48, CD200, and TNFRSF14) were higher in the low-risk group. In addition, patients in the low-risk group were more sensitive to Rucaparib, Navitoclax and Crizotinib than those in the high-risk group. Conclusion: We established a novel necroptosis-related lncRNA based signature to predict prognosis, tumor microenvironment and response to treatment in cervical cancer. Our study provides clues to tailor prognosis prediction and individualized immunization/targeted therapy strategies.

YTHDF2 inhibit the tumorigenicity of endometrial cancer via downregulating the expression of IRS1 methylated with m6A.

RNA epigenetic modification take part in many biology processes, and the N6-methyladenosine (m6A) methylation of specific mRNAs in endometrial cancer (EC) tissues play a key role in regulating the tumorigenicity of EC, but the specific mechanism still unknown and need to be investigated in the future. Here, we found that m6A reader protein YTHDF2 expression was significantly upregulated in EC compare to tumor adjacent tissues, YTHDF2 was then identified to inhibit the proliferation and invasion of EC cell lines. Mechanistically, the m6A reader YTHDF2 bind the methylation sites of target transcripts IRS1 and promoted IRS1 mRNA degradation, consequently inhibiting the expression of IRS1 and inhibiting IRS1/AKT signaling pathway, finally inhibit the tumorigenicity of EC. Thus, we demonstrated that YTHDF2 inhibited the proliferation and invasion of EC via inhibiting IRS1 expression in m6A epigenetic way, which suggests a potential therapeutic target for EC.

ALKBH5 regulates IGF1R expression to promote the Proliferation and Tumorigenicity of Endometrial Cancer.

N6-methyladenosine (m6A) messenger RNA methylation play important role in cell proliferation and tumorigenicity of endometrial cancer, but the key mechanism is not fully clear. Here, we found that RNA demethylase ALKBH5 expression was significantly upregulated in endometrial cancer, ALKBH5 was then identified to positively regulate proliferation and invasion of endometrial cancer. Mechanistically, the m6A eraser ALKBH5 demethylated target transcripts IGF1R and enhanced IGF1R mRNA stability, consequently promoting IGF1R translation and activating IGF1R signaling pathway. Thus, we demonstrated that ALKBH5 promoted proliferation and invasion of endometrial cancer via erasing IGF1R m6A-modifications, which suggests a potential therapeutic target for endometrial cancer.

Photodynamic therapy combined with carbon dioxide laser for low-grade vaginal intraepithelial neoplasia: A retrospective analysis.

OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with a carbon dioxide laser (CO2 laser + PDT) versus CO2 laser for the treatment of low-grade vaginal intraepithelial neoplasms (vaginal LSIL). METHODS: We recruited 40 patients with vaginal LSIL and persistent HR-HPV infection and divided these individuals into two groups. The CO2 laser + PDT group (20 patients) received one CO2 laser treatment and three treatments of ALA-PDT over a one-week interval. The CO2 laser group (20 patients) received up to three CO2 laser treatments. All patients were followed up at 1 month, 3 month, 6 month and 1 year. Hybrid capture HPV DNA assay and colposcopic biopsy were performed for both groups before treatment and during each of the follow-ups. Adverse effects were also assessed. RESULTS: The complete remission (CR) rates were 65 % (13/20) in the CO2 laser group and 85 % (17/20) in the CO2 laser + PDT group (p > 0.05). HR-HPV remission rates were 25 % (5/20) in the CO2 laser group and 95 % (19/20) in the CO2 laser + PDT group (p < 0.05) at one year after treatment. In the CO2 laser group, one patient experienced severe bleeding during treatment. Twelve patients had varying degrees of adhesions and vaginal scar stenosis. One patient underwent vaginal "dead angle" after repeated CO2 laser treatment. No severe adverse events or systemic side effects were observed in the CO2 + PDT group. CONCLUSION: Topical ALA-PDT combined with CO2 laser is an effective, safe, and well-tolerated treatment for vaginal LSIL and HR-HPV infections.

Correlative analysis of the expression of IL-10 and Ki-67 in human cervical cancer and cervical intraepithelial neoplasias and human papillomavirus infection.

This study investigated the expression of IL-10 and Ki-67 in human cervical cancer and cervical intraepithelial neoplasia (CIN) and the correlation with human papillomavirus infection. A total of 110 patients with cervical lesions undergoing surgical treatment in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine from 2016 to 2017 were selected. Those patients included 36 cases of cervical cancer and 74 cases of CIN. At the same time, 30 cases of chronic cervicitis were selected as the control group. RT-qPCR was used to detect the expression of IL-10 and Ki-67 in cervical tissue. PCR was used to detect HPV infection in cervical tissue. The expression levels of IL-10 and Ki-67 in the cervical cancer and CIN groups were higher than those in the control group. Moreover, the expression levels of IL-10 and Ki-67 in the cervical cancer and CIN II-III groups were higher than those in the CIN I group (P<0.05). In addition, the expression levels of IL-10 and Ki-67 in the cervical cancer group were significantly higher than those in the CIN II-III group. Furthermore, the expression levels of IL-10 and Ki-67 were positively correlated with HPV infection (r=0.783 or 0.712, P<0.05). Finally, the expression levels of IL-10 and Ki-67, and HPV infection in the cervical lesions studied were significantly different. Therefore, combined detection of IL-10, Ki-67 and HPV infection can improve the diagnosis of CIN and early cervical cancer.

Polymorphisms of the interleukin 6 gene and additional gene-gene interaction contribute to cervical cancer susceptibility in Eastern Chinese women.

PURPOSE: To investigate the association between IL-6 gene polymorphism and cervical cancer risk, and the impact of multiple gene-gene interaction on cervical cancer risk based on a Chinese Han population. METHODS: A total of 1088 women were selected, including 360 cervical cancer patients and 728 control subjects. Logistic regression model was used to examine the association between SNPs within IL-6 and cervical cancer risk. Odds ratio (OR) and 95 % confident interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the gene-gene interaction. RESULTS: Cervical cancer risks were significantly higher in carriers of C allele of rs1800795 polymorphism than those with GG genotype (GC+CC versus GG), adjusted OR (95 % CI) 1.60 (1.24-2.19), and also significantly higher in carriers of G allele of rs2069837 polymorphism than those with AA (AG+GG versus AA), adjusted OR (95 % CI) 1.49 (1.19-2.07). GMDR analysis found a significant gene-gene interaction between rs1800795 and rs2069837 (p = 0.0010). Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 61.72 %. We also calculated the odds ratios and 95 % CI for this interaction, and we found that subjects with GC or CC of rs1800795 and AG or GG of rs2069837 genotype have the highest cervical cancer risk, compared to subjects with GG of rs1800795 and AA of rs2069837 genotype, OR (95 % CI) 3.35 (2.01-4.78). CONCLUSIONS: Minor allele of rs1800795 and rs2069837 and its interaction were associated with increased cervical cancer risk.