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Background: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA)., Methods: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5'-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case-control analysis, we developed a diagnostic model for NPC, and validated its detection capability., Findings: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%-100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage., Interpretation: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC., Funding: A full list of funding bodies that contributed to this study can be found in Funding section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method., Methods and Patients: All 76 women undergoing Intensity-Modulated Radiation Therapy (IMRT) were included in this study. Patients were immobilized in a supine position using a vacuum bag and thermoplastic cast formation. In the trial group (n = 36), patients raised their buttocks and a solid foam pad was placed under the sacral tail before immobilization. The control group (n = 40) received treatment in the standard supine position. The SB was delineated from the pubic symphysis to the total iliac bifurcation in computed tomography (CT) scans., Result: In the trial group, a significant reduction in SB volume within the pelvic cavity was observed (mean 399.17 ± 158.7 cc) compared to the control group (mean 547.48 ± 166.9 cc), with a p-value less than 0.001. The trial group showed a statistically significant reduction in the absolute volume of irradiated SB at each dose, ranging from the low dose (10 Gy) to the high dose (45 Gy). In the control group, a negative correlation was found between SB and bladder volumes (R = -0.411, P = 0.008), whereas in the trial group, this correlation was weaker (R = -0.286, P = 0.091), with no significant relationship observed between bladder volume and SB., Conclusion: The high buttocks supine position effectively reduces SB radiation exposure without the need for bladder distension. This positioning method holds promise for reducing SB irradiation in various pelvic tumors., (© 2024. The Author(s).)

Background: It remains controversial whether the application of chemotherapy has an impact on recurrent nasopharyngeal carcinoma (rNPC) patients with salvage radiotherapy. Here, we aimed to evaluate treatment outcomes of rNPC patients and derive a prognostic model to assess the benefit of chemotherapy in patients with re-radiotherapy. Methods: This study was conducted as a retrospective study. In total, 340 rNPC patients treated with salvage intensity-modulated radiotherapy (IMRT) or radiochemotherapy (RCT) from October 2006 to September 2019 were included in this study. Overall survival (OS) was the primary outcome. Kaplan-Meier method was employed to detect the prognostic difference with Log-rank tests. The Cox regression analysis was performed to explore the potential prognostic factors while the multivariate Cox analysis was used to identify candidate variables for the prognostic model of OS. Results: The 5-year actuarial rates of OS, progression-free survival, loco-regional progression-free survival, and distant metastases-free survival did not show significant difference between the IMRT and RCT groups ( P  > .05). Age at recurrence and rT category were found to be the independent prognostic factors for OS. We found that rNPC patients suffered poor OS in the high-risk group (patients with higher age at recurrence and advanced rT category) (high-risk vs low-risk, HR = 1.87, 95% CI: 1.36-2.57, P  < .001). Salvage RT alone may be superior to RCT for patients in the low-risk group (RCT group vs RT group, HR = 1.89, 95% CI: 1.11-3.20, P  = .038). Conclusion: Salvage RT combined with chemotherapy cannot improve survival outcomes for rNPC. More novel clinical trials should be explored to develop individualized strategies to improve survival and minimize toxicities.

Responses from the paired organs are generally highly correlated in bilateral studies, statistical procedures ignoring the correlation could lead to incorrect results. Note the intraclass correlation in the study of combined unilateral and bilateral outcomes; 11 confidence intervals (CIs) including 7 asymptotic CIs and 4 Bootstrap-resampling CIs for assessing the equivalence of 2 treatments are derived under Rosner's correlated binary data model. Performance is evaluated with respect to the empirical coverage probability (ECP), the empirical coverage width (ECW) and the ratio of the mesial non-coverage probability to the non-coverage probability (RMNCP) via simulation studies. Simulation results show that (i) all CIs except for the Wald CI and the bias-corrected Bootstrap percentile CI generally produce satisfactory ECPs and hence are recommended; (ii) all CIs except for the bias-corrected Bootstrap percentile CI provide preferred RMNCPs and are more symmetrical; (iii) as the measurement of the dependence increases, the ECWs of all CIs except for the score CI and the profile likelihood CI show increasing patterns that look like linear, while there is no obvious pattern on the ECPs of all CIs except for the profile likelihood CI. A data set from an otolaryngologic study is used to illustrate the proposed methods., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 Informa UK Limited, trading as Taylor & Francis Group.)

Interferon γ (IFN-γ), a multifunctional cytokine, was upregulated in the resected gastric cancer tissue. However, whether IFN-γ is involved in the regulation of gastric cancer has not been well elucidated. Herein, we aimed to investigate the effects and mechanism of IFN-γ on gastric cancer. In this study, we found a vital role of IFN-γ in enhancing proliferation, inhibiting apoptosis, and promoting cell migration and invasion in gastric cancer cells SGC-7901 and MGC-803. Additionally, IFN-γ activated nuclear factor κB (NF-κB) signaling pathway by upregulating the phosphorylation expression of p65 and IκBα, and induced the expression of integrin β3 in vitro. Therefore, to further investigate the relationship between IFN-γ and integrin β3, SGC-7901 cells were transfected with integrin β3 siRNA. And then cells expressed lower cell viability, migration, and invasion rates, while cell apoptosis was significantly enhanced. Meanwhile, expression of integrin β3, MMP-2, MMP-9, and NF-κB, including p65 and IκBα, and the nuclear translocation of NF-κB/p65 were dramatically repressed, whereas IFN-γ significantly improved the effects. Moreover, in vivo, the experiment of xenograft model and pulmonary metastasis model also retarded in integrin β3 siRNA group. And the expression of integrin β3, MMP-2, MMP-9, and NF-κB was repressed. However, the treatment with IFN-γ improved tumor volume, lung/total weight, tumor nodules, and the protein expression described above compared with integrin β3 siRNA group. Overall, the results indicated that IFN-γ induces gastric cancer cell proliferation and metastasis partially through the upregulation of integrin β3-mediated NF-κB signaling. Hence, the inhibition of IFN-γ or integrin β3 may be the key for the treatment of gastric cancer., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset sporadic Alzheimer disease. Emerging evidence demonstrates a hippocampus-associated learning and memory deficit in aged APOE4 human carriers and also in aged mice carrying human APOE4 gene. This suggests that either exogenous APOE4 or endogenous APOE4 alters the cognitive profile and hippocampal structure and function. However, little is known regarding how Apoe4 modulates hippocampal dendritic morphology, synaptic function, and neural network activity in young mice., Aim: In this study, we compared hippocampal dendritic and spine morphology and synaptic function of young (4 months) mice with transgenic expression of the human APOE4 and APOE3 genes., Methods: Hippocampal dendritic and spine morphology and synaptic function were assessed by neuronal imaging and electrophysiological approaches., Results: Morphology results showed that shortened dendritic length and reduced spine density occurred at hippocampal CA1 neurons in Apoe4 mice compared to Apoe3 mice. Electrophysiological results demonstrated that in the hippocampal CA3-CA1 synapses of young Apoe4 mice, basic synaptic transmission, and paired-pulse facilitation were enhanced but long-term potentiation and carbachol-induced hippocampal theta oscillations were impaired compared to young Apoe3 mice. However, both Apoe genotypes responded similarly to persistent stimulations (4, 10, and 40 Hz for 4 seconds)., Conclusion: Our results suggest significant alterations in hippocampal dendritic structure and synaptic function in Apoe4 mice, even at an early age., (© 2017 John Wiley & Sons Ltd.)

Human hypothalamic hamartoma (HH) is a rare developmental malformation often characterized by gelastic seizures, which are refractory to medical therapy. Ictal EEG recordings from the HH have demonstrated that the epileptic source of gelastic seizures lies within the HH lesion itself. Recent advances in surgical techniques targeting HH have led to dramatic improvements in seizure control, which further supports the hypothesis that gelastic seizures originate within the HH. However, the basic cellular and molecular mechanisms of epileptogenesis in this subcortical lesion are poorly understood. Since 2003, Barrow Neurological Institute has maintained a multidisciplinary clinical program to evaluate and treat patients with HH. This program has provided a unique opportunity to investigate the basic mechanisms of epileptogenesis using surgically resected HH tissue. The first report on the electrophysiological properties of HH neurons was published in 2005. Since then, ongoing research has provided additional insights into the mechanisms by which HH generate seizure activity. In this review, we summarize this progress and propose a cellular model that suggests that GABA-mediated excitation contributes to epileptogenesis in HH lesions., (© 2014 John Wiley & Sons Ltd.)

The Homo erectus cranium from Gongwangling, Lantian County, Shaanxi Province is the oldest fossil hominin specimen from North China. It was found in 1964 in a layer below the Jaramillo subchron and was attributed to loess (L) L15 in the Chinese loess-palaeosol sequence, with an estimated age of ca. 1.15 Ma (millions of years ago). Here, we demonstrate that there is a stratigraphical hiatus in the Gongwangling section immediately below loess 15, and the cranium in fact lies in palaeosol (S) S22 or S23, the age of which is ca. 1.54-1.65 Ma. Closely spaced palaeomagnetic sampling at two sections at Gongwangling and one at Jiacun, 10 km to the north, indicate that the fossil layer at Gongwangling and a similar fossil horizon at Jiacun were deposited shortly before a short period of normal polarity above the Olduvai subchron. This is attributed to the Gilsa Event that has been dated elsewhere to ca. 1.62 Ma. Our investigations thus demonstrate that the Gongwangling cranium is slightly older than ca. 1.62 Ma, probably ca. 1.63 Ma, and significantly older than previously supposed. This re-dating now makes Gongwangling the second oldest site outside Africa (after Dmanisi) with cranial remains, and causes substantial re-adjustment in the early fossil hominin record in Eurasia., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: To explore the independent prognostic factors for the recurrence/metastasis of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC)., Materials and Methods: A total of 604 patients initially diagnosed as LANPC by pathohistology in Fujian Provincial Cancer Hospital were selected to analyze the relationship between the clinical pathological patterns, therapeutic protocols and clinical stages with the recurrence/metastasis of LANPC., Results: The 1-, 3- and 5-year locoregionally recurrent rates of LANPC patients were 2.0%, 9.5% and 12.9% respectively, with average recurrent period being 78 months. Univariate analysis results indicated that clinical stages had certain influence on the recurrent period of LANPC patients. However, COX regression models showed that ages, genders and clinical stages were not the independent prognostic factors influencing the recurrence. The 1-, 3- and 5-year metastatic rates of LANPC patients were 6.6%, 17.5% and 18.8% respectively, with average metastatic period of 73 months. Univariate analysis results demonstrated that ages, N stages, clinical stages, locations of lymph node, retropharyngeal lymph node and extracapsular invasion of lymph node had certain influence on the metastatic period of LANPC patients. Additionally, further COX regression analysis results suggested that T stages, reduction protocols and extracapsular invasion of lymph node were the independent prognostic factors influencing the metastasis of patients with LANPC, in which T stages and extracapsular invasion of lymph node were the pestilent factors while reduction protocols the protective factor., Conclusions: Induction chemotherapy is beneficial to LANPC patients with initial treatment, and the metastatic rate decreases greatly after the application of reduction chemotherapy.

The aim of this study was to evaluate the long-term survival outcomes in patients with advanced thymic carcinoma and identify prognostic factors influencing the survival. We retrospectively analyzed 90 consecutive patients with pathologically confirmed advanced thymic carcinoma (Masaoka III and IV) in our institute, from December 2000 to 2012. Age, sex, clinical characteristics, laboratory findings, Masaoka and tumor node metastasis staging, pathologic grade, and treatment modalities were analyzed to identify prognostic factors associated with the progress-free survival (PFS) and the overall survival (OS) rates. Statistical analysis was conducted using SPSS, version 19.0 (SPSS, Inc, Chicago, IL). A total of 73 (81.1%) male and 17 (18.9%) female patients participated in the study. The median follow-up time was 75 months (range, 20-158 months). The 5-year PFS and OS rates were 23.6% (95% confidence interval [CI], 14.6%-33.8%) and 35.7% (95% CI, 25.1%-46.4%), respectively. The multivariate Cox regression model analysis showed that factors improving the PFS were the normal lactate dehydrogenase (LDH) level (P<0.001), Masaoka III stage (P=0.028), and radiotherapy (RT) (P<0.001). The LDH (P<0.001), T stage (P<0.001), and the pathologic grade (P=0.047) were independently prognostic of OS. Long-term follow-up of the advanced thymic carcinoma showed poor outcomes of PFS and OS. LDH, Masaoka stage, and RT affected the PFS, and LDH, T stage, and pathologic grade seemed to affect the OS. Establishing a better staging system for predicting outcomes would be warranted.

Background: Bone morphogenetic protein-2 (BMP-2) plays a key role both in vascular development and pathophysiological processes. However, the effects of oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin on BMP-2 expression are entirely unknown in human umbilical vein endothelial cells (HUVECs). The present study investigates the effects of ox-LDL on BMP-2 expression. Furthermore, the influence of atorvastatin on ox-LDL-induced BMP-2 expression is also examined., Methods and Results: The HUVECs were treated by ox-LDL or combined with pyrrolidine dithiocarbamate (PDTC) or atorvastatin. The expression level of BMP-2 mRNA was examined by real-time PCR and RT-PCR analysis. The expression of BMP-2 protein was assayed by enzyme-linked immunosorbent assay. The malondialdehyde (MDA) and activities of total superoxide dismutase (SOD) were detected by routine methods. The activation of nuclear factor kappaB (NF-kappaB) in HUVECs was determined using an assay kit from active motif and western blot analysis. Ox-LDL treatment significantly increased BMP-2 expression, which is associated with NF-kappaB activation, but BMP-2 expression was suppressed by treatment with PDTC or atorvastatin. Furthermore, the increase in MDA levels and decrease in activities of total SOD caused by ox-LDL treatment were reversed by the treatment of PDTC or atorvastatin., Conclusions: Ox-LDL-induced BMP-2 expression was suppressed by PDTC or atorvastatin treatment. The effects of atorvastatin might contribute to the mechanisms by inhibiting NF-kappaB activation.