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Objective: To construct models of high-risk human papillomavirus (HPV) infection with precancerous lesions or cervical cancer and explore the immune function. Methods: Using CRISPR/Cas9, the expression vector HPV16-E6-E7-Rosa26 was microinjected into fertilized eggs of C57BL/6 N mice using homologous recombination, and the F0 generation was obtained for reproduction. Then, the formation of precancerous lesions was promoted via intramuscular injection of estradiol. Presence of precancerous cervical-vaginal intraepithelial lesions, Ki67 and p16 expression levels, and CD8+ T cell proportions in the spleen were evaluated. Results: Two F0 generation mice exhibited correct the homologous recombination. Seven positive mice were identified in the F1 generation. After breeding and mating, 25 homozygous and 11 heterozygous HPV16-E6-E7-engineered mice were obtained from the F2 generation. After estradiol benzoate treatment, the cervical-vaginal epithelium appeared as precancerous lesions with positive Ki67 and p16 expression. The percentage of CD8+ T cells decreased. Conclusion: HPV16-E6-E7-Rosa26 induced low immune function in mice, and provides a good model for the basic research of the mechanisms of action of HPV infection-associated precancerous lesions or cervical cancer.

Objective To investigate the survival outcomes and risk factors of patients with stage ⅡB cervical cancer undergoing neoadjuvant chemotherapy (NACT) followed by laparoscopic radical hysterectomy (LRH). Methods A retrospective cohort study was conducted on 178 patients with stage ⅡB cervical cancer who underwent NACT followed by LRH in our department from 2015 to 2018. COX regression analysis was used to analyze the surgical pathological characteristics, and stratified analysis was performed according to the results. Kaplan-Meier survival curve analysis and log-Rank test were employed to analyze the survival outcomes of different subgroups. Results For the 178 subjected patients, their median follow-up period was 51 months, and the rates of 3-year disease-free survival (DFS) and overall survival (OS) were 75.4% and 82.6%, respectively. COX regression analysis showed that lymph node metastasis (LNM) (HR: 2.04, 95%CI: 1.16~3.60) and deep stromal invasion (DSI) (HR: 4.72, 95%CI: 2.11~10.60) were independent risk factors for DFS. LNM (HR: 2.77, 95%CI: 1.48~5.22), DSI (HR: 4.24, 95%CI: 1.64~10.98) and tumor diameter ≥4 cm after NACT (HR: 2.12, 95%CI: 1.14~3.94) were independent risk factors for OS. The rates of 3-year DFS of patients with and without LNM was 55.3% and 81.0% (P < 0.001), and the rates of 3-year OS was 64.8% and 87.7% (P < 0.001), respectively. The rates of 3-year DFS of patients with and without DSI were 64.1% and 92.8% (P < 0.001), and the rates of 3-year OS were 73.2% and 95.7% (P < 0.001), respectively. There was no significant difference in DFS between patients with tumor diameter < 4 cm and ≥4 cm after NACT, while the rates of 3-year OS was 85.1% and 74.4%, respectively (P=0.028). The DFS and OS of patients with tumor diameter reduction >50% after NACT were significantly better than those ≤50% (the 3-year DFS rate: 92.9% vs 71.0%, P < 0.001; the 3-year OS rate: 93.0% vs 82.4%, P=0.017). Conclusion Patients with stage ⅡB cervical cancer with tumor diameter reduced by >50% after NACT have better survival outcomes. LNM, DSI and tumor diameter ≥4 cm after NACT are independent risk factors for the prognosis of stage ⅡB cervical cancer.

Objective To explore the role and mechanism of serum response factor (SRF) in differentiation of rat bone marrow mesenchymal stem cells (MSCs) into bladder smooth muscle cells (SMCs). Methods Rat MSCs and SMCs were isolated respectively from the bone marrow and bladder of 4-week-old female SD rats by adherent method, and then co-cultured together in a Transwell chamber. After the MSCs were harvested at different time points, real-time PCR and immunofluorescense assay were used to detect the expression of SMCs specific marker genes in co-cultured MSCs. Furthermore, the enrichment of histone acetylation modification, histone deacetylase (HDAC) and SRF in the promoter of these genes were tested by chromatin immunoprecipitation assay (ChIP) q-PCR in co-cultured MSCs. Finally, ChIP-qPCR was used to compare the histone acetylation modification and SRF enrichment in sodium butyrate (NaB) pretreatment group with control cells. Results The expression levels of α-SMA, Calponin and SM-MHC were increased in MSCs co-cultured with SMCs. H3K9ace, H3ace and H4ace in the promoter of these genes were enriched (P

Large igneous provinces (LIPs) are often the surface expressions of mantle plume process. Intensive magma could occur in the continental crust when a mantle plume penetrates the Moho. How magmas migrate in the crust, forming LIPs, remains debated. In this study, we employ 2D thermo‐mechanical numerical modelling to study the dynamics of magma intrusion and migration within the continental crust affected by a mantle plume. Our results suggest that (1) lateral magma migration dominates crustal deformation, promoting the possible formation of metamorphic core complexes; (2) two distinct crustal deformation modes are recognized regarding the presence or absence of crustal break‐up, affected by whether a significant vertical magma migration occurs; (3) the crustal thickness, Moho temperature and the length of the preset weak crust–mantle decoupling zone are the three key parameters controlling crustal magma migration. This study highlights the importance of lateral magma migration in the lower crust and provides physical mechanisms for the interpretation of magma migration under LIPs. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of folate receptor 1(FOLR1) and mesothelin (MSLN) in epithelial ovarian cancer(EOC) and explore their clinical significance. Methods The data of clinical samples and transcriptome sequencing expression matrix of EOC were obtained from TCGA and GEO database(Ovarian Cancer TCGA, Provisional; GSE6008; GSE66957; GSE49997) to analyze the expressions of FOLR1 and MSLN in different tissues and their association with tumor staging and the prognosis of EOC. We also collected paraffin-embedded tissue samples of EOC(105 cases), ovarian borderline tumor(11 cases), and normal ovarian tissue(30 cases) from patients undergoing surgeries in our hospital between 2018 and 2019. The expression levels of FOLR1 and MSLN were detected by immunohistochemistry and their correlation with the clinicopathological characteristics of the patients was analyzed. Results Analysis of TCGA and GEO databases showed that the mRNA levels of FOLR1 and MSLN were significantly higher in EOC tissues than in normal ovarian tissues(P < 0.05), and was also higher in stage Ⅲ~Ⅳ than in stage Ⅰ~Ⅱ EOC(P < 0.05). Survival analysis showed that the patients with a high expression of FOLR1 had significantly longer overall survival(P < 0.05) and disease-free survival(P < 0.05), while the patients with a high expression of MSLN had significantly shortened overall survival(P < 0.05) and disease-free survival(P < 0.05). Immunohistochemical analysis showed that FOLR1 and MSLN proteins were lowly expressed in normal ovarian tissues, and their expressions increased moderately in borderline ovarian tumor and significantly in EOC tissues. The positive expression rates of FOLR1 and MSLN in EOC were 80.95% and 53.33%, respectively. The levels were of FOLR1 and MSLN differed significantly in different tissue types(P < 0.001), and their positive rates were significantly higher in stage Ⅲ~Ⅳ than in stage Ⅰ~Ⅱ EOC(P < 0.05). The positive rate of MSLN was significantly increased in patients with lymph node metastasis(P < 0.05). Subgroup survival analysis of TCGA database showed that patients with a low MSLN expression and a high FOLR1 expression(MLFH) at the mRNA level had the best prognosis, while those with a high MSLN expression and a low FOLR1 expression(MHFL) had the worst prognosis(median survival time 70.57 vs 25.85 months, P < 0.000 1); compared with the MLFL patients, the MHFL patients in the early stage(< 50 months) had a better prognosis, while beyond 50 months, the survival rate of the patients decreased, but the difference was not statistically significant. Conclusion In patients with EOC, a high expression of FOLR1 indicates a more favorable prognosis while a high expression of MSLN is associated with a poor prognosis. These 2 proteins may participate in the process of EOC, and their combined detection may help in prognostic evaluation of EOC.

This study proposed a novel method based on self-interference polarisation pantograph (SiPPer) for fabricating Pancharatnam-Berry (PB) devices. The SiPPer method was composed of a standard Cassegrainian system and a polarization patterned template. Based on the self-interference effect between the ordinary and extraordinary components after the birefringence template, all the polarization information were losslessly transferred to the focal plane on which a photosensitive polarization sample was placed. All PB devices are compatible with this method, including polarization grating, q-plate, q-lens, etc. The SiPPer method indeed lowers the requirement on the exposing source, particularly on the parameters of coherence length and linewidth. To verify and evaluate the properties of the SiPPer method, two typical examples, liquid crystal polarization grating and q-plate, were designed and fabricated according to the standard processing. And the experimental results showed fabulous agreement with the theoretical simulation results. [ABSTRACT FROM AUTHOR]