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This study aimed to develop and validate nomograms for improving overall survival (OS) and cancer-specific survival (CSS) predictions in elderly patients diagnosed with vulvar squamous cell carcinoma (VSCC). Data from the Surveillance, Epidemiology, and End Results (SEER) database were retrieved to gather information on VSCC patients aged 60 years and older. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors. Based on these factors, nomograms were constructed to predict patients' OS and CSS. Model accuracy and discriminative power were assessed using the concordance index (C-index), area under the receiver operating characteristic curve (AUC), and calibration curves. Decision curve analysis (DCA) was also employed to assess the clinical significance of the proposed nomograms in comparison to the TNM (Tumor Node Metastasis) and AJCC (American Joint Committee on Cancer) staging systems. Between 2000 and 2019, a total of 2736 elderly VSCC patients met the inclusion criteria and were randomly divided into two groups: a training set (N = 1927) and a validation set (N = 809). Independent risk factors for predicting OS included age, grade, summary stage, T stage, N stage, primary site surgery, chemotherapy, regional node status and tumor size. For predicting CSS, independent risk factors were age, summary stage, AJCC stage, T stage, N stage, primary site surgery, chemotherapy, regional node status and tumor size. The C-index for OS in the training and validation sets was 0.724 (95% CI: 0.710-0.738) and 0.73 (95% CI: 0.708-0.752), respectively. In contrast, for CSS prediction, the C-index was 0.758 (95% CI: 0.740-0.776) in the training set and 0.774 (95% CI: 0.749-0.799) in the validation set. The proposed nomograms for predicting OS and CSS in VSCC patients aged 60 and older demonstrate promising potential as reliable tools that clinicians can consider to make more informed therapeutic decisions. [ABSTRACT FROM AUTHOR]

This study aimed to develop a nomogram for estimating the overall survival (OS) of vulvar squamous cell carcinoma patients aged =50 years based on their clinicopathological characteristics. The Surveillance, Epidemiology and End Results (SEER) database was searched for cases diagnosed with vulvar squamous cell carcinoma from 2000 to 2019. They were randomly grouped into a training and a test cohort in a 7:3 ratio. Cox regression analyses were performed to identify risk factors associated with the overall survival rate of the patients. Then, the nomogram was built based on independent factors selected by the minimum Akaike Information Criterion (AIC) value in multivariate Cox regression analyses. The performance of the nomogram was assessed by its concordance index (C-index) and the area under curve (AUC). Its predictive power was determined by calibration plot and clinical applicability by decision curve analysis (DCA). A total of 3048 patients were identified and randomized into the training (n = 2146) and validation (n = 902) cohort. The validation indicated that the nomogram had good recognition ability for clinical trials, patient counseling, and rationalizing therapeutic modalities. The C-index for OS rates was 0.729 (95% Confidence Interval (CI): 0.715-0.743) in the training cohort and 0.717 (95% CI: 0.693- 0.741) in the validation cohort. The AUCs of the 1-, 3- and 5-year OS were 0.789, 0.781 and 0.775 in the training cohort and 0.815, 0.772 and 0.748 in the validation cohort. Calibration plots showed that the nomogram had good predictive power, and DCA demonstrated that the proposed nomogram could provide a net clinical benefit. Our nomogram demonstrated promising accuracy in comprehensively predicting the OS of elderly vulvar squamous cell carcinoma patients. It could be used as a reference to guide individualized treatments and plan the follow-up of elderly patients with vulvar squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

this research analyses 10 universities from the United Kingdom and China respectively to make a comparison between TESOL and TCSOL curriculum. Based on the analysis, the compulsory courses, and optional courses, some similarities and differences have been analyzed. By referring to the curriculum of TESOL, some suggestions have been put forward. This research aims to inject broader approaches to the study of Master of Teaching Chinese to Speakers of Other Language (TCSOL), which would result in an enhanced understanding and enlargement of the subject matter, provide new thinking direction, promote the development of TCSOL, and reduce the possible confusion on the future development. [ABSTRACT FROM AUTHOR]

In this paper, a new class of five parameter gamma-exponentiated or generalized modified Weibull (GEMW) distribution which includes exponential, Rayleigh, Weibull, modified Weibull, exponentiated Weibull, exponentiated exponential, exponentiated modified Weibull, exponentiated modified exponential, gamma-exponentiated exponential, gammaexponentiated Rayleigh, gamma-modified Weibull, gamma-modified exponential, gamma-Weibull, gamma-Rayleigh and gamma-exponential distributions as special cases is proposed and studied. Mathematical properties of this new class of distributions including moments, mean deviations, Bonferroni and Lorenz curves, distribution of order statistics and Renyi entropy are presented. Maximum likelihood estimation technique is used to estimate the model parameters and applications to real data sets presented in order to illustrate the usefulness of this new class of distributions and its sub-models. [ABSTRACT FROM AUTHOR]

Background: Targeting the TGF-β1 pathway for breast cancer metastasis therapy has become an attractive strategy. We have previously demonstrated that naringenin significantly reduced TGF-β1 levels in bleomycin-induced lung fibrosis and effectively prevented pulmonary metastases of tumors. This raised the question of whether naringenin can block TGF-β1 secretion from breast cancer cells and inhibit their pulmonary metastasis.Methods: We transduced a lentiviral vector encoding the mouse Tgf-β1 gene into mouse breast carcinoma (4T1-Luc2) cells and inoculated the transformant cells (4T1/TGF-β1) into the fourth primary fat pat of Balb/c mice. Pulmonary metastases derived from the primary tumors were monitored using bioluminescent imaging. Spleens, lungs and serum (n = 18-20 per treatment group) were analyzed for immune cell activity and TGF-β1 level. The mechanism whereby naringenin decreases TGF-β1 secretion from breast cancer cells was investigated at different levels, including Tgf-β1 transcription, mRNA stability, translation, and extracellular release.Results: In contrast to the null-vector control (4T1/RFP) tumors, extensive pulmonary metastases derived from 4T1/TGF-β1 tumors were observed. Administration of the TGF-β1 blocking antibody 1D11 or naringenin showed an inhibition of pulmonary metastasis for both 4T1/TGF-β1 tumors and 4T1/RFP tumors, resulting in increased survival of the mice. Compared with 4T1/RFP bearing mice, systemic immunosuppression in 4T1/TGF-β1 bearing mice was observed, represented by a higher proportion of regulatory T cells and myeloid-derived suppressor cells and a lower proportion of activated T cells and INFγ expression in CD8(+) T cells. These metrics were improved by administration of 1D11 or naringenin. However, compared with 1D11, which neutralized secreted TGF-β1 but did not affect intracellular TGF-β1 levels, naringenin reduced the secretion of TGF-β1 from the cells, leading to an accumulation of intracellular TGF-β1. Further experiments revealed that naringenin had no effect on Tgf-β1 transcription, mRNA decay or protein translation, but prevented TGF-β1 transport from the trans-Golgi network by inhibiting PKC activity.Conclusions: Naringenin blocks TGF-β1 trafficking from the trans-Golgi network by suppressing PKC activity, resulting in a reduction of TGF-β1 secretion from breast cancer cells. This finding suggests that naringenin may be an attractive therapeutic candidate for TGF-β1 related diseases. [ABSTRACT FROM AUTHOR]