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Objective:To investigate the factors influencing the prognosis of anaplastic thyroid cancer (ATC) and to evaluate the application value of established random survival forest (RSF) model in the prognosis prediction of ATC.Methods:A total of 707 ATC patients diagnosed by histopathology in the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute from 2004 to 2015 were selected and randomly divided into the training set (495 cases) and the validation set (212 cases). Univariate Cox regression risk model was used to analyze the related factors affecting overall survival (OS) of patients in the training set. The multivariate Cox proportional risk model based on the minimum Akaike information criterion (AIC) was used to analyze the above variables and then the variables were screened out. The traditional Cox model for predicting OS was constructed based on the screened variables. The RSF algorithm was used to analyze the variables with P < 0.05 in the univariate Cox regression analysis, and 5 important features were selected. Multivariate Cox proportional risk model was selected based on the minimum AIC. Then the RSF-Cox model for predicting OS was constructed by using screened variables. The time-dependent receiver operating characteristic (tROC) curve and the area under the curve (AUC), calibration curve, decision curve and integrated Brier score (IBS) in the training set and the validation set were used to evaluate the prediction performance of the models. Results:Univariate Cox regression analysis showed that age, chemotherapy, lymph node metastasis, radiotherapy, surgical method, tumor infiltration degree, tumor number, tumor diameter and diagnosis time were factors affecting the prognosis of ATC (all P < 0.05). Multivariate Cox regression analysis based on minimal AIC (4 855.8) showed that younger age (61-70 years vs. > 80 years: HR = 0.732, 95% CI 0.56-0.957, P = 0.023; ≤ 50 years vs. > 80 years: HR = 0.561, 95% CI 0.362-0.87, P = 0.010), receiving chemotherapy (receiving or not: HR = 0.623, 95% CI 0.502-0.773, P < 0.001), receiving radiotherapy (receiving or not: HR = 0.695, 95% CI 0.559-0.866, P = 0.001), receiving surgery (lobectomy, no surgery or unknown: HR = 0.712, 95% CI 0.541-0.939, P = 0.016; total resection or subtotal resection vs. no surgery or unknown: HR = 0.535, 95% CI 0.436-0.701, P < 0.001), and tumor diameter (≤ 2 cm vs. > 6 cm: HR = 0.495, 95% CI 0.262-0.938, P = 0.031; > 2 cm and ≤ 4 cm vs. > 6 cm: HR = 0.714, 95% CI 0.520-0.980, P = 0.037; > 4 cm and ≤ 6 cm vs. > 6 cm: HR = 0.699, 95 % CI 0.545-0.897, P = 0.005) were independent protective factors for OS of ATC patients. Lymph node metastasis (N 1 unknown vs. N 0: HR = 1.664, 95% CI 1.158-2.390, P = 0.006; N 1b: HR = 1.312, 95% CI 1.029-1.673, P = 0.028), more aggressive tumor infiltration degree (group 3 vs. group 1: HR = 1.492, 95% CI 1.062-2.096, P = 0.021; group 4 vs. group 1: HR = 1.636, 95% CI 1.194 - 2.241, P = 0.002) were independent risk factors for OS of ATC patients. Although diagnosis time was not statistically significant (2010-2015 vs.2004-2009: HR = 1.166, 95% CI 0.962-1.413, P = 0.118), the inclusion of it could improve the efficacy of the traditional Cox model. RFS algorithm was used to select out 5 important variables: surgical method, tumor diameter, age group, chemotherapy, and tumor number. Multivariate Cox regression analysis based on minimum AIC (4 884.6) showed that chemotherapy (receiving or not: HR = 0.574, 95% CI 0.476-0.693, P < 0.001), surgical method (lobectomy, no surgery or unknown: HR = 0.730, 95% CI 0.567-0.940, P = 0.015; total resection or subtotal resection vs. no surgery or unknown: HR = 0.527, 95% CI 0.423-0.658, P < 0.001), tumor diameter (≤ 2 cm vs. > 6 cm: HR = 0.428, 95% CI 0.231-0.793, P = 0.007; > 2 cm and ≤ 4 cm vs. > 6 cm: HR = 0.701, 95% CI 0.513-0.958, P = 0.026; > 4 cm and ≤ 6 cm vs. > 6 cm: HR = 0.681, 95% CI 0.536-0.866, P = 0.002) were independent factors for OS of ATC patients. RSF-Cox model was constructed based on 3 variables. The tAUC curve analysis showed that RSF-Cox model for predicting the 6-month, 12-month, and 18-month OS rates were 93.56, 92.62, and 90.80, respectively in the training set, and 93.05, 92.47, and 90.20, respectively in the validation set; in the traditional Cox model, the corresponding OS rates were 89.00, 87.76, 85.24, respectively in the training set, and 86.22, 83.68, 82.86, respectively in the validation set. When predicting OS rate at 6-month, 12-month and 18-month, the calibration curve of RSF-Cox model was closer to 45° compared with that of traditional Cox model, and the clinical net benefit of decision curve in RSF-Cox model was higher than that in traditional Cox model. The IBS of RSF-Cox model (0.089) was lower than that of traditional Cox model (0.111). Conclusions:The RSF model based on chemotherapy, surgical method and tumor diameter can effectively predict the OS of ATC patients.
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Objective To investigate the relationship between lymph nodes count after selective neck lymph node dissection and the prognosis of patients with pathologically lymph node-negative (pN0) hypopharyngeal squamous cell carcinoma (HPSCC). Methods The clinical data of 96 patients with pN0 HPSCC undergoing selective neck dissection (bilateralⅡ-Ⅳregion) from October 1995 to October 2012 in Shanxi Provincial Cancer Hospital were analyzed retrospectively. The optimal lymph nodes count cutoff values were determined by using the X-tile program in different prognostic groups, and the univariate and multivariate survival analysis in different groups were analyzed by using SPSS 19.0 software. Results A total of 2116 lymph nodes were detected in this cohort, with a median number of 22 (3-52). Except for the tumor site (P= 0.011), there were no statistical differences in lymph nodes count of patients with different age, gender, history of smoking or drinking, T stage, and differentiation degree (all P> 0.05). Applying 9 and 23 nodes as the cutoff values determined by using X-tile program, all patients could be divided into the high-risk (13 cases, lymph nodes count 3-9), the middle-risk (37 cases, lymph nodes count 10-22) and the low-risk (46 cases, lymph nodes count 23-52) groups. And the 5-year overall survival (OS) rate was 23.1 %, 55.9%and 86.0%in the high, middle, low risk groups respectively (χ2= 21.73, P< 0.001). Multiple-factor analysis showed that lymph nodes count, T stage and degree of tumor differentiation were independent prognostic factors in patients with pN0 HPSCC (all P< 0.05). Further analysis showed that when the cutoff value of lymph nodes count was 9, the patients could be divided into two groups with significantly differentprognosis. The 5-year OS rate was 23.1% in the high-risk group and 73.2 % in the low-risk group, and the difference was statistically significant (χ2 = 17.87, P< 0.001). Conclusions Lymph nodes count after selective neck lymph node dissection can be used to predict the prognosis of patients with pN 0 HPSCC. It is likely that 9 is the minimum number of lymph nodes in pN0 HPSCC patients.
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The boomerang-like H subunit of A(1)A(0) ATP synthase forms one of the peripheral stalks connecting the A(1) and A(0) sections. Structural analyses of the N-terminal part (H1-47) of subunit H of the A(1)A(0) ATP synthase from Methanocaldococcus jannaschii have been performed by NMR spectroscopy. Our initial NMR structural calculations for H1-47 indicate that amino acid residues 7-44 fold into a single alpha-helical structure. Using the purified N- (E1-100) and C-terminal domains (E101-206) of subunit E, NMR titration experiments revealed that the N-terminal residues Met1-6, Lys10, Glu11, Ala15, Val20 and Glu24 of H1-47 interact specifically with the N-terminal domain E1-100 of subunit E. A more detailed picture regarding the residues of E1-100 involved in this association was obtained by titration studies using the N-terminal peptides E1-20, E21-40 and E41-60. These data indicate that the N-terminal tail E41-60 interacts with the N-terminal amino acids of H1-47, and this has been confirmed by fluorescence correlation spectroscopy results. Analysis of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the central stalk subunit F in the presence and absence of E101-206 show no obvious interaction between the C-terminal domain of E and subunit F. The data presented provide, for the first time, structural insights into the interaction of subunits E and H, and their arrangement within A(1)A(0) ATP synthase.
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Complejos de ATP Sintetasa/química , Complejos de ATP Sintetasa/metabolismo , Methanococcaceae/enzimología , Complejos de ATP Sintetasa/genética , Complejos de ATP Sintetasa/aislamiento & purificación , Secuencia de Aminoácidos , Expresión Génica , Methanococcaceae/genética , Modelos Moleculares , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Unión Proteica , Estructura Cuaternaria de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/genética , Subunidades de Proteína/aislamiento & purificación , Subunidades de Proteína/metabolismo , Espectrometría de Fluorescencia , VolumetríaRESUMEN
Objective To discuss the treatment effect of well-differentiated thyroid carcinoma.Methods From 1992 to 2002,42 cases of well-differentiated thyroid carcinoma invading the laryngotrachea were treated in shanxi tumor hospital.Radical tumor resection were 6 cases,local shaving-off tumor resection were 32 cases and incomplete tumor resection were 4 cases.Some patients received postoperative radiotheraPy.Results In the 42patients,the overall 5-year survival rates were 76.2%(32/42).Conclusion Although well-differentiated thyroid carcinoma invaded the laryngotrachea,the operation can increase the curative effect and the patient's living standand.