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Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.
Subject(s)
Male , Humans , Prognosis , Neoplasm Recurrence, Local/pathology , Prostatic Neoplasms/pathology , Prostatectomy , Drug Resistance , Aldehyde Dehydrogenase, MitochondrialABSTRACT
OBJECTIVE: To explore the value of the 8 th edition of the AJCC staging system in evaluating the prognosis of patients with intrahepatic cholangiocarcinoma(ICC) after operation.METHODS: A total of 155 patients with ICC after radical resection in Eastern Hepatobiliary Surgery Hospital,Naval Military Medical University from January 2013 to December 2018 were analyzed retrospectively.All patients were staged according to the 8 th edition of the AJCC staging system.The survival rates were estimated using Kaplan-Meier methods.Multivariate analysis was assessed by Cox proportional hazards regression analysis.The predictive ability of staging systems was evaluated by receiver operating characteristic curve(ROC) and area under curve(AUC).RESULTS:(1) The follow-up rate of 155 patients was 70.3%,and the median follow-up time was 26(1-67) months.The 1-,3-,and 5-year survival rates of patients after surgery were81%,39%,and 25%,respectively.(2) The median survival time of T1 a,T1 b,T2,T3,and T4 stages was 45.5,28.8,19.1,18.9 and 16.2 months,respectively(P<0.001);The median survival time of N0 and N1 stages was 33.4 and 15.8 months,respectively(P<0.001);The median survival time of ⅠA,ⅠB,Ⅱ,Ⅲ A and Ⅲ B stages was 46.8,32.3,21.6,20.3 and 15.6 months,respectively(P<0.001).The ROC curve analysis of T stage,N stage and TNM stage indicated that the AUC were0.704,0.718 and 0.698,respectively.(3) Univariate analysis indicated that CA19-9,tumor number,vascular invasion,intraoperative blood transfusion,T stage,N stage and TNM stage were risk factors for prognosis in patients with ICC(P<0.05).Multivariate analysis indicated that the number of tumors,intraoperative blood transfusion,and N stage were independent risk factors for prognosis in patients with ICC(P<0.05).CONCLUSION: The 8 th edition of the AJCC staging system is of certain value in the evaluation of postoperative prognosis of intrahepatic cholangiocarcinoma.Multiple tumors,intraoperative blood transfusion and N stage are independent prognostic factors for ICC patients.
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To discuss the advantages and necessity of hidden curriculum construction in the academic experience inheritance of distinguished TCM veteran doctors by analyzing the characteristics of the hidden curriculum and the academic experience inheritance of distinguished TCM veteran doctors, and put forward viewpoints and pathways of promoting academic experience inheritance of distinguished TCM veteran doctors through the construction of hidden curriculum，such as optimal design of teaching environment，reasonable planning of teaching content and development of teaching information model，to effectively improve student cultivation quality and achieve the TCM talent cultivation goal which clinical diagnosis and treatment skills and clinical innovation ability are the core.
Subject(s)
Humans , Curriculum , Medicine, Chinese Traditional , PhysiciansABSTRACT
<p><b>BACKGROUND</b>Nuclear mitotic apparatus protein 1 (NuMA1) had been reported to produce three groups of isoforms categorized as long, middle, and short groups, of which short NuMA displayed distinct localization patterns compared to long and middle isoforms. However, the function of short NuMA was not clear in the progress of cancer formation. This study aimed to unveil the role of short NuMA in cancer pathogenesis.</p><p><b>METHODS</b>The expression levels of short isoforms were explored in paired gastric carcinoma (GC) samples and different cell lines. Furthermore, the short isoform behaved as a putative tumor suppressor based on cell proliferation and cell colony formation assays. Pull-down assay and whole-genome gene expression analysis were carried out to search candidate interaction partners of short NuMA.</p><p><b>RESULTS</b>The expression of short NuMA was highly expressed in S and G2 phases of the cell cycle; compared with nontumor tissues, short NuMA downregulated in nine GCs (GC1 [0.131, P = 5 × 10-4]; GC2 [0.316, P = 3 × 10-5]; GC3 [0.111, P = 6 × 10-4]; GC4 [0.456, P = 0.011]; GC5 [0.474, P = 0.001]; GC6 [0.311, P = 0.004]; GC7 [0.28, P = 3 × 10-5]; GC8 [0.298, P = 0.007]; and GC9 [0.344, P = 0.002]). Besides, high expression of short NuMA significantly inhibits cell growth (2.43 × 105 vs. 2.97 × 105, P = 0.0029) and cell clone information in vitro (70 vs. 2, P = 1.67 × 10-45). Short NuMA could bind with alpha-actinin-4 (ACTN4), a putative tumor promoting gene. Overexpression of short NuMA could tremendously decrease the expression of MYB proto-oncogene like 2 (MYBL2) of about 92-fold, which played an important role in the cell cycles.</p><p><b>CONCLUSIONS</b>Short isoform of NuMA might be functioned as a putative role of tumor suppressor. Further studies should be made to illuminate the relationship between ACTN4, MYBL2, and tumor progression.</p>
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Objective To investigate the typical value of gamma-radiation dose rate and its confidence interval in tank-transported copper ore by using bootstrap resampling techniques. Methods Bootstrap resampling method, coupled with kernel density estimation, introduced to acquire the typical value of gamma-radiation dose rate in copper ore. Results The typical value of gamma-radiation dose rate in copper ore was expressed as the central tendency of the means of resampling, and two kinds of confidence interval, empirical percentile and bias-corrected accelerated confidence interval, were provided as standard error. Conclusion It is clearly demonstrated that this method has an advantage to give a robust description in explanation of central tendency and variation range of gamma-radiation dose rate data profiles.