TIP60 mediates stress-induced hypertension via promoting glutamatedmPFC-to-vCA1 release.

Hypertension is well-known to be influenced by genetic and environmental factors. Managing stress is one of the non-pharmacologic approaches to treating hypertension. It is, therefore, imperative to unravel the molecular mechanism by which stress conditions influence hypertension. In this study, TIP60 expressions in human blood samples and cell lines, glutamatedmPFC-to-vCA1 release, and receptor expressions in the Stress-induced hypertension mice were determined using western blotting, CSF (obtained by microdialysis), and ELISA. The study reports increased protein expressions of TIP60 in the peripheral blood of hypertensive patients and in cell lines representing hypertension. In Chronic restraint stress (CRS) conditions TIP60 expression and vCA1 glutamate release were found to be up-regulated, with high SBP and DSP indicating hypertension was induced. After electrical stimulation at the dmPFC, release of glutamate in the vCA1 increased, indicating that activity within the dmPFC drives the release of glutamate in the vCA1, which was blocked by injecting MG149 (a TIP60 inhibitor) into dmPFC. To further determine whether TIP60 was involved in glutamate release and eventually results in hypertension, MG149 was also injected i.p. alongside CRS modeling. The increased glutamate release, NR2B, and IL-18 expressions as well as the CRS-induced hypertension was therefore reversed by chronic application with MG149. Altogether, these results suggest that TIP60 influences the glutamatedmPFC-to-vCA1 release and receptor expressions. This study, therefore, proposes that stressful condition induces increased expression of TIP60 which lead to the transcription of genes that result in conditions that favors glutamate release and receptor expressions hence triggering hypertension.

Thermoelectric Rectification and Amplification in Interacting Quantum-Dot Circuit-Quantum-Electrodynamics Systems.

Thermoelectric rectification and amplification were investigated in an interacting quantum-dot circuit-quantum-electrodynamics system. By applying the Keldysh nonequilibrium Green's function approach, we studied the elastic (energy-conserving) and inelastic (energy-nonconserving) transport through a cavity-coupled quantum dot under the voltage biases in a wide spectrum of electron-electron and electron-photon interactions. While significant charge and Peltier rectification effects were found for strong light-matter interactions, the dependence on electron-electron interaction could be nonmonotonic and dramatic. Electron-electron interaction-enhanced transport was found under certain resonance conditions. These nontrivial interaction effects were found in both linear and nonlinear transport regimes, which manifested in charge and thermal currents, rectification effects, and the linear thermal transistor effect.

TIP60 buffers acute stress response and depressive behaviour by controlling PPARγ-mediated transcription.

Tat-interacting protein 60 (TIP60) as nuclear receptors (NRs) coregulator, acts as a tumor suppressor and also has promising therapeutic potential to target Alzheimer's disease. Stress has been implicated in many psychiatric disorders, and these disorders are characterized by impairments in cognitive function. Until now, there are no experimental data available on the regulatory effect of TIP60 in acute stress and depression. There is also no definitive explanation on which specific modulation of target gene expression is achieved by TIP60. Here, we identify TIP60 as a novel positive regulator in response to acute restraint stress (ARS) and a potentially effective target of antidepressants. Firstly, we discovered increased hippocampal TIP60 expressions in the ARS model. Furthermore, using the TIP60 inhibitor, MG149, we proved that TIP60 function correlates with behavioral and synaptic activation in the two-hour ARS. Secondly, the lentivirus vector (LV)-TIP60overexpression (OE) was injected into the hippocampus prior to the chronic restraint stress (CRS) experiments and it was found that over-expressed TIP60 compensates for TIP60 decrease and improves depression index in CRS. Thirdly, through the intervention of TIP60 expression in vitro, we established the genetic regulation of TIP60 on synaptic proteins, confirmed the TIP60 function as a specific coactivator for PPARγ and found that the PPARγ-mediated TIP60 function modulates transcriptional activation of synaptic proteins. Finally, the LV-TIP60OE and PPARγ antagonist, GW9662, were both administered in the CRS model and the data indicated that blocking PPARγ significantly weakened the protective effect of TIP60 against the CRS-induced depression. Conclusively, these findings together support TIP60 as a novel positive factor in response to acute stress and interacts with PPARγ to modulate the pathological mechanism of CRS-induced depression.

Ionizing Aromatic Compounds in Petroleum by Electrospray with HCOONH4 as Ionization Promoter.

Electrospray ionization (ESI) coupled with Fourier ion cyclotron resonance mass spectrometry (FTICR MS) has been successfully used for molecular characterization of petroleum. However, ESI can not ionize nonpolar components which generally are dominant in the petroleum fraction. Here, we introduce a novel approach for aromatic compounds molecular characterization. Aromatics in petroleum fractions were ionized to [M + H](+) by positive-ion ESI with HCOONH4 as an ionization promoter, and when ESI is combined with high resolution FTICR MS, aromatic hydrocarbons and heteroatoms in petroleum fractions can be simultaneously analyzed. The method is easily available and has potential for the characterization of aromatic compounds in any other matrix.

Liquid metal biomaterials: translational medicines, challenges and perspectives.

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal (LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity, and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc. Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed. Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety, material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

Grating-based x-ray dark-field CT for lung cancer diagnosis in mice.

BACKGROUND: The low absorption of x-rays in lung tissue and the poor resolution of conventional computed tomography (CT) limits its use to detect lung disease. However, x-ray dark-field imaging can sense the scattered x-rays deflected by the structures being imaged. This technique can facilitate the detection of small alveolar lesions that would be difficult to detect with conventional CT. Therefore, it may provide an alternative imaging modality to diagnose lung disease at an early stage. METHODS: Eight mice were inoculated with lung cancers simultaneously. Each time two mice were scanned using a grating-based dark-field CT on days 4, 8, 12, and 16 after the introduction of the cancer cells. The detectability index was calculated between nodules and healthy parenchyma for both attenuation and dark-field modalities. High-resolution micro-CT and pathological examinations were used to crosscheck and validate our results. Paired t-test was used for comparing the ability of dark-field and attenuation modalities in pulmonary nodule detection. RESULTS: The nodules were shown as a signal decrease in the dark-field modality and a signal increase in the attenuation modality. The number of nodules increased from day 8 to day 16, indicating disease progression. The detectability indices of dark-field modality were higher than those of attenuation modality (p = 0.025). CONCLUSIONS: Compared with the standard attenuation CT, the dark-field CT improved the detection of lung nodules. RELEVANCE STATEMENT: Dark-field CT has a higher detectability index than conventional attenuation CT in lung nodule detection. This technique could improve the early diagnosis of lung cancer. KEY POINTS: • Lung cancer progression was observed using x-ray dark-field CT. • Dark-field modality complements with attenuation modality in lung nodule detection. • Dark-field modality showed a detectability index higher than that attenuation in nodule detection.

Recurrence risk model for esophageal cancer after radical surgery.

OBJECTIVE: The aim of the present study was to construct a risk assessment model which was tested by disease-free survival (DFS) of esophageal cancer after radical surgery. METHODS: A total of 164 consecutive esophageal cancer patients who had undergone radical surgery between January 2005 and December 2006 were retrospectively analyzed. The cutpoint of value at risk (VaR) was inferred by stem-and-leaf plot, as well as by independent-samples t-test for recurrence-free time, further confirmed by crosstab chi-square test, univariate analysis and Cox regression analysis for DFS. RESULTS: The cutpoint of VaR was 0.3 on the basis of our model. The rate of recurrence was 30.3% (30/99) and 52.3% (34/65) in VaR <0.3 and VaR ≥0.3 (chi-square test, (χ) (2) =7.984, P=0.005), respectively. The 1-, 3-, and 5-year DFS of esophageal cancer after radical surgery was 70.4%, 48.7%, and 45.3%, respectively in VaR ≥0.3, whereas 91.5%, 75.8%, and 67.3%, respectively in VaR <0.3 (Log-rank test, (χ) (2) =9.59, P=0.0020), and further confirmed by Cox regression analysis [hazard ratio =2.10, 95% confidence interval (CI): 1.2649-3.4751; P=0.0041]. CONCLUSIONS: The model could be applied for integrated assessment of recurrence risk after radical surgery for esophageal cancer.

Long-Term Social Isolation-Induced Autophagy Inhibition and Cell Senescence Aggravate Cognitive Impairment in D(+)Galactose-Treated Male Mice.

Aging is associated with physiological and pathological changes and presents health complications, such as dementia. Isolation has also been associated with the experience of growing old. Both have been linked individually to the incidence of cognitive decline. In this present study, the effects of these two phenomena have been looked at in animal models where aging was induced with D(+)Galactose in mice who underwent long-term post-weaned social isolation (L-PWSI). Assessing cognitive function using Y-maze, Morris water maze (MWM), and passive avoidance tests (PATs) confirmed that cognition is impaired in either of the treatments but worsened when the D(+)Galactose mice were subjected to L-PWSI. Moreover, a synaptic protein, PSD95, and dendritic spines density were significantly reduced in the L-PWSI and D(+)Galactose-treated mice. Our previous study revealed that autophagy deficit is involved in cognitive impairment in the L-PWSI model. Here, we first report the inhibited cell cycle in L-PWSI, combined with the decreased autophagy, aggravates cognitive impairment in D(+)Galactose-treated mice. Beyond these, the autophagy and cell cycle mechanisms that link isolation and aging have been explored. The close association between isolation and aging in humans is very real and needs much research attention going forward for possible therapeutic interventions.

Two-hour acute restraint stress facilitates escape behavior and learning outcomes through the activation of the Cdk5/GR P S211 pathway in male mice.

Acute stress exerts pleiotropic actions on learning behaviors. The induced negative effects are sometimes adopted to measure the efficacy of particular drugs. Until now, there are no detailed experimental data on the time-gradient effects of acute stress. Here, we developed the time gradient acute restraint stress (ARS) model to precisely assess the roles of different restrain times on inducing acute stress. Time gradient ARS facilitates escape behaviors and learning outcomes, peaking at 2 h-ARS and then declining to baseline at 3.5 h-ARS as confirmed by time gradient post-stress data. Furthermore, time gradient ARS activates glucocorticoid receptor (GR) phosphorylation site at Serine211 (P S221) as an inverted V-shaped pattern peaking at 2 h-ARS, whereas that of the GR phosphorylation site at Serine226 (P S226) from 2 h-ARS to 3.5 h-ARS. The 2 h-ARS but not 3.5 h-ARS enhances synaptic plasticity and genes transcription associated with learning and memory in the hippocampus of male mice. The Cdk5 inhibitor, roscovitine, blocks this facilitation effect by intervening in GR phosphorylation at Serine211 in the 2 h-ARS mice. Altogether, these findings show that the time gradient ARS selectively activates GR phospho-isoforms and differentially influences the behaviors along with maintaining a relationship between 2 h-ARS and Cdk5/GR P S211-mediated transcriptional activity.

Extracellular HMGB1 augments macrophage inflammation by facilitating the endosomal accumulation of ALD-DNA via TLR2/4-mediated endocytosis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unclear pathogenesis. We previously reported that syngenetic, activated lymphocyte-derived DNA (ALD-DNA) could robustly elicit macrophage activation, which plays an important role in the pathogenesis of murine lupus nephritis. In addition, extracellular HMGB1 obviously facilitated the accumulation of ALD-DNA in endosomes and promoted macrophage inflammation. While the detailed mechanism was still unknown. In this study, we found that HMGB1 could obviously change the DNA uptake pathways in macrophages. ALD-DNA alone was mainly uptake by the low efficient and unselective macropinocytosis, while extracellular HMGB1 potently promoted the more efficient and specific clathrin-/caveolin-1-dependent receptor-mediated endocytosis pathways, and led to the rapid and abundant aggregation of ALD-DNA in endosomes. This effect relied on the DNA binding ability and TLR2/TLR4 of HMGB1. Our study not only helped us to understand the promotion mechanisms of extracellular HMGB1 on ALD-DNA-induced macrophage inflammation, but also provided some clues to the pathogenesis of SLE.

Prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery.

The aim of this study was to retrospectively analyze and assess the outcomes and prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. One hundred twenty-six patients with node-positive thoracic esophageal squamous cell carcinoma who had undergone adjuvant therapy (postoperative radiotherapy alone or postoperative sequential chemoradiotherapy without receiving postoperative concurrent chemoradiotherapy) after radical surgery, were retrospectively reviewed from January 1996 to December 2003. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves were estimated using the Kaplan-Meier method. The 1-, 3- and 5-year overall survival rates of all 126 patients were 71.4, 39.1, and 22.0%, and disease-free survival rates were 64.3, 36.4, and 21.5%, respectively. Lymph node ratio (the ratio of the number of metastatic lymph nodes to the number of lymph nodes removed, LNR) > or = 0.2 (P= 0.006), pT3 + pT4 (P= 0.06) and sequential chemoradiotherapy (P= 0.08) were associated with a poorer survival by univariate analysis. In multivariate analysis, LNR (P= 0.01, hazard ratio = 0.57, 95% confidence interval, 0.37-0.87) and tumor depth of invasion (P= 0.03, hazard ratio = 0.62, 95% confidence interval, 0.41-0.96) were the independent predictors of survival. Sequential chemoradiotherapy receded survival tendency without significant difference (P= 0.09, hazard ratio = 0.64, 95% confidence interval, 0.37-1.08). Therefore, LNR and tumor depth of invasion were the independent prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. The addition of chemotherapy does not seem to confer a survival benefit.

Compositional Characterization of Expelled and Residual Oils in the Source Rocks from Oil Generation-Expulsion Thermal Simulation Experiments.

Petroleum generation-expulsion thermal simulation experiments on a low-maturity type I source rock were carried out. The composition of hydrocarbons and heteroatom-containing compounds in both expelled and residual oils was characterized by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and gas chromatography-mass spectrometry. A thorough analysis of fractionation effects was presented between expelled and residual oils. The oil composition strongly depended on the pyrolysis temperature. A significant difference in the molecular composition was found between expelled and residual oils at various pyrolysis temperatures. The difference in maturity for expelled and residual oils could be revealed clearly by the difference in the molecular composition of heteroatom-containing compounds. Carboxylic acids in the residual oil cracked quickly with the pyrolysis temperature above 350 °C (% Ro = 1.0) but part of them would survive if they were expelled out of the source rock timely. The variations between the relative abundance of oxygen compounds and nitrogen compounds indicated that the thermostability of oxygen-containing nitrogen compounds was lower than that of neutral nitrogen compounds. The variation trends in double bond equivalents and carbon number distributions of O1, O2, and N1 class species were similar. The aromaticity of heteroatom-containing polar species increased with maturity.

Alterations in Brain Structural Connectivity After Unilateral Upper-Limb Amputation.

Previous studies have indicated that amputation induces reorganization of functional brain network. However, the influence of amputation on structural brain network remains unclear. In this study, using diffusion tensor imaging (DTI), we aimed to investigate the alterations in fractional anisotropy (FA) network after unilateral upper-limb amputation. We acquired DTI from twenty-two upper-limb amputees (15 dominant-side and 7 nondominant-side amputees) as well as fifteen healthy controls. Using DTI tractography and graph theoretical approaches, we examined the topological changes in FA network of amputees. Compared with healthy controls, dominant-side amputees showed reduced global mean strength, increased characteristic path length, and decreased nodal strength in the contralateral sensorimotor system and visual areas. In particular, the nodal strength of the contralateral postcentral gyrus was negatively correlated with residual limb usage, representing a use-dependent reorganization. In addition, the nodal strength of the contralateral middle temporal gyrus was positively correlated with the magnitude of phantom limb sensation. Our results suggested a degeneration of FA network after dominant-side upper-limb amputation.

DNA methylation and transcriptome signature of the IL12B gene in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is an autoimmune disease without a reliable biomarker. This study investigated the IL12B gene methylation as a robust marker by integrating DNA methylation and mRNA data. METHODS: A two-stage design was used for methylome and transcriptome investigation. The first phase detected methylation level from 99 AS patients and 99 healthy controls (HCs) whilst the second phase measured mRNA level from 20 patients and 20 HCs. We conducted analysis of differential methylation sites and receiver operating characteristic (ROC) as well as mRNA level to verify methylation. RESULTS: We investigated 37 methylation sites that were mapped to 2 CpG islands (IL12B-1 and IL12B-2). Compared with HCs, the two islands were hypermethylated (IL12B-1: P = 4.6 ∗ 10 ^ -4; IL12B-2: P = 1.3 ∗ 10 ^ -5) and the mRNA level was overexpressed (P = 0.004) in AS patients. The subgroup analysis results showed a significant hypermethylation of the two islands in B27 positive group (IL12B-1: P = 3.7 ∗ 10 ^ -4; IL12B-2: P = 3.7 ∗ 10 ^ -6) and in male patients (IL12B-1: P = 4.9 ∗ 10 ^ -4; IL12B-2: P = 7.2 ∗ 10 ^ -6). ROC results found that the IL12B-1 island had a sensitivity of 62.6% and a specificity of 66.7%, and the IL12B-2 had a sensitivity of 50.0% and a specificity of 77.7%. CONCLUSION: DNA methylation and transcriptome signature of the IL12B gene can discriminate AS patients from HCs, and hypermethylation of the IL12B may contribute to the pathogenesis of AS.

Nonlinear effects for three-terminal heat engine and refrigerator.

The three-terminal heat device that consists of an electronic cavity and couples to a heat bath is studied both as a heat engine and as a refrigerator. We investigate the characteristic performance in the linear and nonlinear regime for both setups. It is our focus here to analyze how the efficiency of the heat engine and coefficient of performance of the refrigerator are affected by the nonlinear transport. With such considerations, the maximum efficiency and power are then optimized for various energy levels, temperatures and other parameters.

Autophagy inhibition enhances radiosensitivity of Eca­109 cells via the mitochondrial apoptosis pathway.

Autophagy inhibition is crucial for the improvement of the efficacy of radiotherapy in cancer. The aim of the present study was to determine the potential therapeutic value of autophagy and its correlation with mitochondria in human esophageal carcinoma cells following treatment with ionizing radiation (IR). Autophagy in Eca­109 cells was induced under poor nutrient conditions. The formation of autophagic vacuoles was monitored using electron microscopy. In addition, cell apoptosis after IR and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. LC3, beclin­1, cytochrome c and apoptosis-related proteins were assayed by western blotting. A nude mouse xenograft model was also employed to verify the biological effects and mechanisms underlying autophagy in vivo. The formed autophagic vesicles and increased LC3 II/LC3 I ratio indicated marked induction of autophagy by Earle's balanced salt solution (EBSS) in Eca­109 cells. 3­Methyladenine or LY294002 significantly antagonized EBSS-induced autophagy and increased apoptosis of irradiated cells, suggesting that autophagy inhibition conferred radiosensitivity in vitro. Notably, IR induced prominent release of cytochrome c and Bax activation, and decreased Bcl-2 and MMP expression in Eca­109 cells under poor nutrient conditions. Of note, these changes were more prominent following pretreatment with autophagy inhibitors. In vivo, IR treatment mildly delayed tumor growth, but the radiotherapeutic effect was improved significantly by abolishing autophagy. Furthermore, mitochondrial signaling was investigated in the Eca­109 xenograft nude mice model, and the results were consistent with the in vitro study. Therefore, the mitochondrial pathway may be associated with improvement of radiosensitivity in Eca­109 cells.

Salvage radiochemotherapy for lymph node recurrence after radical surgery of esophageal cancer.

To evaluate the efficacy of salvage radiochemotherapy (SRC) in patients with recurrent lymph node after radical surgery in esophageal cancer.This study enrolled 58 patients with esophageal squamous cell carcinoma who underwent SRC for lymph node recurrence after radical surgery from August 2011 to November 2015 at our hospital. Survival rates were calculated by the Kaplan-Meier method with the log-rank test. Multivariate analysis was conducted using the Cox model.The overall 1-, 3-, and 5-year survival rates after radical surgery were 94.8%, 53.0%, and 29.6%, respectively. The 1- and 3-year survival rates after SRC were 68.7% and 26.9%, respectively. The major acute toxicities were esophagitis and neutropenia, while most toxicities were grade 1 or 2. There was no unexpected increase in serious adverse events or treatment-related deaths. The results of multivariate analysis showed that time to recurrence (odds ratio [OR]: 0.25, 95% confidence interval [CI]: 0.11-0.53, P = .0004), T stage (OR: 2.75, 95%CI: 1.16-6.49, P = .021), and prophylactic radiotherapy/chemotherapy (PRC, OR: 0.39, 95%CI: 0.16-0.98, P = .045) were determinants of postoperative overall survival, and PRC was the only factor affecting the outcome of SRC (OR: 0.28, 95%CI: 0.12-0.70, P = .006).SRC is an effective treatment for recurrent lymph node after radical surgery of esophageal cancer.

Phase II Trial of Intensity-Modulated Radiotherapy Concurrent With Chemotherapy for Postoperative Node-Positive Esophageal Squamous Cell Carcinoma.

The aim of this study was to evaluate the efficacy and toxicity of intensity-modulated radiotherapy concurrent with weekly docetaxel in patients with node-positive esophageal squamous cell carcinoma after radical surgery. Between January 2011 and December 2013, a total of 46 eligible patients were enrolled. All patients received intensity-modulated radiotherapy concurrent with weekly docetaxel (20 mg/m2). Patients were treated 5 days per week at 2.0 Gy/day. The total dose of external radiotherapy given was 50 Gy in 25 fractions. The primary endpoints included treatment completion and safety. The secondary endpoint was to assess whether the approach would achieve a 1-year survival rate of 80% or higher. The median duration of follow-up was 18 months (range: 2-41 months). The 1-year overall survival and progression-free survival rate were 91.2% and 80.4%, respectively. The major acute toxicities were esophagitis and neutropenia. While most cases were grade 1 or 2, grade 3 neutropenia and esophagitis were observed in seven (15.2%) and five patients (10.9%), respectively. The toxicities were controllable and transitory. There were no unexpected cases of serious adverse events or treatment-related deaths. Our study confirms that intensity-modulated radiotherapy with concurrent weekly docetaxel is an effective and safe treatment in postoperative node-positive patients with esophageal squamous cell carcinoma. The identified treatment regimen is of interest for a phase III trial.

Staging of nasopharyngeal carcinoma investigated by magnetic resonance imaging.

BACKGROUND AND PURPOSE: To investigate the American Joint Commission on Cancer (AJCC) sixth edition staging system of nasopharyngeal carcinoma (NPC) by Magnetic Resonance Imaging (MRI). PATIENTS AND METHODS: One hundred and fifty-nine non-disseminated biopsy-proven NPC patients were studied with MRI before treatment. Retrieval of MRI information enabled us to restage all patients accurately according to the sixth edition of the AJCC staging system. Splitting the respective T and N stages by the significant defining factors identified, the cancer death hazard ratios were modeled by the Cox model in SPSS 10.0 for windows (SPSS Inc, Chicago, IL). RESULTS: Single site of skull base abnormality (HR = 3.91, 95% CI: 0.74-20.56) has a superior result to others involved in T3 (HR = 5.83, 95% CI: 1.24-27.29). Involvement of either anterior or posterior cranial nerves solely (HR = 6.02, 95% CI: 1.55-35.60) was not found to be as a poor prognostic indicator as others involved in T4 (HR = 7.81, 95% CI: 1.81-33.63). Less than or equal to 3 cm of N1 (HR = 4.01, 95% CI: 0.48-33.83) and N2 (HR = 4.72, 95% CI: 0.62-35.78) have a better result than >3 cm of N1 (HR = 8.09, 95% CI: 0.95-68.97) and N2 (HR = 10.58, 95% CI: 1.32-84.62), respectively. CONCLUSIONS: Perhaps, it is better to down-stage single site of skull base abnormality from T3 to T2, and involvement of either anterior or posterior cranial nerves solely from T4 to T3, meanwhile, < or =3 cm of N2 down-stage to N1, >3 cm of N1 up-stage to N2.

Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal carcinoma.

PURPOSE: To evaluate the influence of skull base bone (SBB) abnormality showed by MRI on prognosis of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From March 1993 to December 1998, 122 NPC patients received prime radiotherapy treatment. All of them were proved pathologically and checked by magnetic resonance imaging (MRI). Every patient received radiation through conjoint facio-cervical field and conventional dose-fractionation schedules. The total dose to the primary tumor was 60-75 Gy (median, 70 Gy). The Kaplan-Meier method, the Log-rank test and the Cox regression model were used to evaluate the significance of prognostic factors on NPC patient survival. RESULTS: The overall median survival period was 50 (6-92) months, and the 1, 3 and 5 year-survival rates were, respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%, 89.8%, 77.0%, respectively (P = 0.4233). Gender, age, head pain, SBB abnormality, cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were analyzed with the Cox regression model and SBB abnormality on MRI did not prove to have statistical significance (P = 0.6934). According to the analysis of regrouping, patients with SBB abnormalities > or =2 sites have a worse prognosis (P = 0.0427). Then, the above seven factors are analyzed by Cox regression model and the result had statistical significance (P = 0.0385). CONCLUSION: The SBB abnormality on MRI is of no obvious influence on prognosis of NPC. However, when SBB abnormality sites were > or =2, there is obvious statistical significance on the prognosis.