Sex differences in methylphenidate-induced dopamine increases in ventral striatum.

Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [11C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of "drug effects" and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).

A dynamic nomogram combining tumor stage and magnetic resonance imaging features to predict the response to induction chemotherapy in locally advanced nasopharyngeal carcinoma.

OBJECTIVES: To establish an effective dynamic nomogram combining magnetic resonance imaging (MRI) findings of primary tumor and regional lymph nodes with tumor stage for the pretreatment prediction of induction chemotherapy (IC) response in locoregionally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 498 LANPC patients (372 in the training and 126 in the validation cohort) with MRI information were enrolled. All patients were classified as "favorable responders" and "unfavorable responders" according to tumor response to IC. A nomogram for IC response was built based on the results of the logistic regression model. Also, the Cox regression analysis was used to identify the independent prognostic factors of disease-free survival (DFS). RESULTS: After two cycles of IC, 340 patients were classified as "favorable responders" and 158 patients as "unfavorable responders." Calibration curves revealed satisfactory agreement between the predicted and the observed probabilities. The nomogram achieved an AUC of 0.855 (95% CI, 0.781-0.930) for predicting IC response, which outperformed TNM staging (AUC, 0.661; 95% CI 0.565-0.758) and the MRI feature-based model alone (AUC, 0.744; 95% CI 0.650-0.839) in the validation cohort. The nomogram was used to categorize patients into high- and low-response groups. An online dynamic model was built ( https://nomogram-for-icresponse-prediction.shinyapps.io/DynNomapp/ ) to facilitate the application of the nomogram. In the Cox multivariate analysis, clinical stage, tumor necrosis, EBV DNA levels, and cervical lymph node numbers were independently associated with DFS. CONCLUSIONS: The comprehensive nomogram incorporating MRI features and tumor stage could assist physicians in predicting IC response and formulating personalized treatment strategies for LANPC patients. KEY POINTS: • The nomogram can predict IC response in endemic LANPC. • The nomogram combining tumor stage with MRI-based tumor features showed very good predictive performance. • The nomogram was transformed into a web-based dynamic model to optimize clinical application.

Regulating Luminescence Thermal Quenching of Praseodymium-Doped Niobo-Tantalate Phosphor through Intervalence Charge Transfer Band Displacement.

Pr3+-related intervalence charge transfer (IVCT) bands are a research hotspot owing to their amelioration in the luminescence thermal quenching of Pr3+-activated phosphors. Here, a typical IVCT band displacement strategy via a topological chemical scheme is reported to optimize the luminescence thermal quenching performance of praseodymium-doped niobo-tantalate. The substitution of Ta5+ ions for Nb5+ ions reduces the valence-weighted average cation optical electronegativity and increases the bond lengths of the activator (Pr3+) to the ligand cations (Nb5+ and Ta5+) via adjusting the crystal structure, leading to an increase in the IVCT energy level position from 3.521 to 4.139 eV. The increase in the IVCT energy level leads to an increase in the number of electrons located in the Pr3+ 3P0 energy level, which compensates for the emission of 1D2 during warming. Especially, the energy gap value of the IVCT band is positively correlated with the thermal quenching activation energy ΔE2. ΔE2 increases, the crossover point rises, and the nonradiative transition decreases, further enhancing the Pr3+ 1D2 emission. At 503 K, the 1D2 emission integral intensity increases from 14 to 224% relative to the 303 K original integral intensity. This IVCT band displacement strategy can be used as a scheme for designing antithermal quenching luminescence materials.

Downregulation of annexin A3 promotes ionizing radiation-induced EGFR activation and nuclear translocation and confers radioresistance in nasopharyngeal carcinoma.

Radioresistance currently poses a significant challenge to successful disease control of nasopharyngeal carcinoma (NPC). We previously uncovered that annexin A3 (ANXA3), a calcium-dependent phospholipid binding protein, is underexpressed in radioresistant NPC cells and mouse xenografts. This study aims to further unravel the mechanistic basis underlying ANXA3-mediated radioresistance in NPC. We show that either innate ANXA3 downregulation or short hairpin RNA(shRNA)-based knockdown of ANXA3 confers resistance to ionizing radiation (IR) in NPC both in vitro and in mouse xenograft models in vivo, whereas radiosensitization was observed when ANXA3 was ectopically expressed. Mechanistically, ANXA3 knockdown dramatically enhances IR-induced epidermal growth factor receptor (EGFR) phosphorylation and nuclear translocation, leading to increased post-IR phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) concomitant with markedly accelerated DNA DSB repair. In addition, pretreatment with cetuximab efficiently abrogated the radioresistant phenotype of ANXA3-low cells as well as the ANXA3 knockdown-induced post-IR EGFR nuclear accumulation, suggesting that EGFR is an essential mediator for ANXA3 depletion-mediated radioprotection in NPC. Collectively, this work reveals for the first time a critical role of ANXA3 in radiation survival and DNA repair mechanism of NPC and provides mechanistic evidence to support ANXA3 as a potential therapeutic target to improve radiocurability for NPC.

Temporal-spatial distributions of road silt loadings and fugitive road dust emissions in Beijing from 2019 to 2020.

Road silt loading (sL) is an important parameter in the fugitive road dust (FRD) emissions. In this study, the improved Testing Re-entrained Aerosol Kinetic Emissions from Roads (TRAKER) combined with the AP-42 method was firstly developed to quickly measure and estimate the sLs of paved roads in Beijing, China. The annual average sLs in Beijing was 0.59±0.31 g/m2 in 2020, and decreased by 22.4% compared with that in 2019. The seasonal variations of sLs followed the order of spring > winter > summer > autumn in the two years. The seasonal mean road sLs on the same type road in the four seasons presented a decline trend from 2019 to 2020, especially on the Express way, decreasing 47.4%-72.7%. The road sLs on the different type roads in the same season followed the order of Major arterial ∼ Minor arterial ∼ Branch road > Express road, and Township road ∼ Country highway > Provincial highway ∼ National highway. The emission intensities of PM10 and PM2.5 from FRD in Beijing in 2020 were lower than those in 2019. The PM10 and PM2.5 emission intensities at the four planning areas in the two years all presented the order of the capital functional core area > the urban functional expansion area > the urban development new area > the ecological conservation and development area. The annual emissions of PM10 and PM2.5 from FRD in Beijing in 2020 were 74,886 ton and 18,118 ton, respectively, decreasing by ∼33.3% compared with those in 2019.

MineBL: A Battery-Free Localization Scheme with Binocular Camera for Coal Mine.

Accurate localization in underground coal mining is a challenging technology in coal mine safety production. This paper proposes a low-cost battery-free localization scheme based on depth images, called MineBL. The main idea is to utilize the battery-free low-cost reflective balls as position nodes and realize underground target localization with a series of algorithms. In particular, the paper designs a data enhancement strategy based on small-target reorganization to increase the identification accuracy of tiny position nodes. Moreover, a novel ranging algorithm based on multi-filter cooperative denoising has been proposed, and an optimized weighted centroid location algorithm based on multilateral location errors has been designed to minimize underground localization errors. Many experiments in the indoor laboratories and the underground coal mine laboratories have been conducted, and the experimental results have verified that MineBL has good localization performances, with localization errors less than 30 cm in 95% of cases. Therefore, MineBL has great potential to provide a low-cost and effective solution for precise target localization in complex underground environments.

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. METHODS: In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18-75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing. FINDINGS: Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3-11·4]) than in the placebo group (median 6·9 months [5·9-7·3]; hazard ratio 0·54 [95% CI 0·39-0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death). INTERPRETATION: Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. FUNDING: Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The endoplasmic reticulum HSP40 co-chaperone ERdj3/DNAJB11 assembles and functions as a tetramer.

ERdj3/DNAJB11 is an endoplasmic reticulum (ER)-targeted HSP40 co-chaperone that performs multifaceted functions involved in coordinating ER and extracellular proteostasis. Here, we show that ERdj3 assembles into a native tetramer that is distinct from the dimeric structure observed for other HSP40 co-chaperones. An electron microscopy structural model of full-length ERdj3 shows that these tetramers are arranged as a dimer of dimers formed by distinct inter-subunit interactions involving ERdj3 domain II and domain III Targeted deletion of residues 175-190 within domain II renders ERdj3 a stable dimer that is folded and efficiently secreted from mammalian cells. This dimeric ERdj3 shows impaired substrate binding both in the ER and extracellular environments and reduced interactions with the ER HSP70 chaperone BiP. Furthermore, we show that overexpression of dimeric ERdj3 exacerbates ER stress-dependent reductions in the secretion of a destabilized, aggregation-prone protein and increases its accumulation as soluble oligomers in extracellular environments. These results reveal ERdj3 tetramerization as an important structural framework for ERdj3 functions involved in coordinating ER and extracellular proteostasis in the presence and absence of ER stress.

Effect of chemotherapy on survival in patients with stage T3-4N0M0 nasopharyngeal carcinoma.

PURPOSE: To identify whether chemoradiotherapy improves survival in patients with stage T3-4N0M0 nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The data of patients with stage T3-4N0M0 NPC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. The patients were divided into radiotherapy and chemoradiotherapy groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method and propensity score matching (PSM) analyses. RESULTS: We examined 496 patients: 88 who received radiotherapy and 408 who received chemoradiotherapy. Before PSM, chemoradiotherapy was associated with a better 5-year OS (52.58% vs. 38.13%; P = .005) and similar CSS (63.62% vs. 59.26%; P = .196) compared to those associated with radiotherapy. However, chemoradiotherapy was not an independent prognostic factor for OS [hazard ratio (HR)=0.95, 95% confidence interval (CI): 0.68-1.32; P = .760] or CSS (HR = 1.02, 95% CI: 0.66-1.56; P = .935). After PSM, similar OS (45.15% vs. 42.78%; P = .626) and CSS (58.22% vs. 60.37%; P = .730) were found between the radiotherapy and chemoradiotherapy groups. CONCLUSION: Radiotherapy and chemoradiotherapy are associated with similar OS and CSS in patients with stage T3-4N0M0 NPC.

Air pollutant emissions from the asphalt industry in Beijing, China.

Improving our understanding of air pollutant emissions from the asphalt industry is critical for the development and implementation of pollution control policies. In this study, the spatial distribution of potential maximum emissions of volatile organic compounds (VOCs) in the complete life cycle of asphalt mixtures, as well as the particulate matter (PM), asphalt fume, nonmethane hydrocarbons (NMHCs), VOCs, and benzoapyrene (BaP) emissions from typical processes (e.g., asphalt and concrete mixing stations, asphalt heating boilers, and asphalt storage tanks) in asphalt mixing plants, were determined in Beijing in 2017. The results indicated that the potential maximum emissions of VOCs in the complete life cycle of asphalt mixtures were 18,001 ton, with a large contribution from the districts of Daxing, Changping, and Tongzhou. The total emissions of PM, asphalt fume, NMHC, VOCs, and BaP from asphalt mixing plants were 3.1, 12.6, 3.1, 23.5, and 1.9 × 10-3 ton, respectively. The emissions of PM from asphalt and concrete mixing stations contributed the most to the total emissions. The asphalt storage tank was the dominant emission source of VOCs, accounting for 96.1% of the total VOCs emissions in asphalt mixing plants, followed by asphalt heating boilers. The districts of Daxing, Changping, and Shunyi were the dominant regions for the emissions of PM, asphalt fume, NMHC, and BaP, while the districts of Shunyi, Tongzhou, and Changping contributed the most emissions of VOCs.

A positive feedback loop between Wnt/ß-catenin signaling and hTERT regulates the cancer stem cell-like traits in radioresistant nasopharyngeal carcinoma cells.

Radioresistance may be induced by cancer stem cells (CSCs), while the biological traits of CSCs need to be retained by telomerase. The telomerase activity mainly depends on the transcriptional regulation of human telomerase reverse transcriptase (hTERT). Moreover, Wnt/ß-catenin signaling is also considered essential for maintaining the CSC phenotypes. In the previous study, we discovered that the radioresistant nasopharyngeal carcinoma cells CNE-2R displayed CSC-like traits, as well as high expression of hTERT and ß-catenin, but whether hTERT and ß-catenin were involved in regulating the CSC-like traits and radiosensitivity of CNE-2R cells remained unclear. In this study, our results suggested that hTERT could positively regulate the expression of CSC-related proteins, as well as the cytoplasm- and nucleus-ß-catenin, but it could not markedly regulate the expression of total ß-catenin in CNE-2R cells. Meanwhile, Wnt/ß-catenin signaling had a positive regulatory effect on the expression of hTERT and CSC-related proteins. Moreover, there was a ß-catenin/hTERT protein complex in CNE-2R cells, indicating that ß-catenin could directly interact with hTERT protein. Our results also revealed that silencing hTERT or suppressing Wnt/ß-catenin signaling could attenuate telomerase activity and radioresistance of CNE-2R cells; while suppressing Wnt/ß-catenin signaling, the telomerase activity and radioresistance could be reversed through overexpressing hTERT. Taken together, we have outlined a positive feedback loop between Wnt/ß-catenin signaling and hTERT in CNE-2R cells, which can regulate the telomerase activity and CSC-like traits, thus regulating the radiosensitivity. Therefore, blocking Wnt/ß-catenin signaling transduction and interfering with hTERT expression may be a promising approach for targeting radioresistant nasopharyngeal carcinoma cells with CSC-like traits.

Unfolded protein response-induced ERdj3 secretion links ER stress to extracellular proteostasis.

The Unfolded Protein Response (UPR) indirectly regulates extracellular proteostasis through transcriptional remodeling of endoplasmic reticulum (ER) proteostasis pathways. This remodeling attenuates secretion of misfolded, aggregation-prone proteins during ER stress. Through these activities, the UPR has a critical role in preventing the extracellular protein aggregation associated with numerous human diseases. Here, we demonstrate that UPR activation also directly influences extracellular proteostasis through the upregulation and secretion of the ER HSP40 ERdj3/DNAJB11. Secreted ERdj3 binds misfolded proteins in the extracellular space, substoichiometrically inhibits protein aggregation, and attenuates proteotoxicity of disease-associated toxic prion protein. Moreover, ERdj3 can co-secrete with destabilized, aggregation-prone proteins in a stable complex under conditions where ER chaperoning capacity is overwhelmed, preemptively providing extracellular chaperoning of proteotoxic misfolded proteins that evade ER quality control. This regulated co-secretion of ERdj3 with misfolded clients directly links ER and extracellular proteostasis during conditions of ER stress. ERdj3 is, to our knowledge, the first metazoan chaperone whose secretion into the extracellular space is regulated by the UPR, revealing a new mechanism by which UPR activation regulates extracellular proteostasis.

Molecular mechanisms of substrate-controlled ring dynamics and substepping in a nucleic acid-dependent hexameric motor.

Ring-shaped hexameric helicases and translocases support essential DNA-, RNA-, and protein-dependent transactions in all cells and many viruses. How such systems coordinate ATPase activity between multiple subunits to power conformational changes that drive the engagement and movement of client substrates is a fundamental question. Using the Escherichia coli Rho transcription termination factor as a model system, we have used solution and crystallographic structural methods to delineate the range of conformational changes that accompany distinct substrate and nucleotide cofactor binding events. Small-angle X-ray scattering data show that Rho preferentially adopts an open-ring state in solution and that RNA and ATP are both required to cooperatively promote ring closure. Multiple closed-ring structures with different RNA substrates and nucleotide occupancies capture distinct catalytic intermediates accessed during translocation. Our data reveal how RNA-induced ring closure templates a sequential ATP-hydrolysis mechanism, provide a molecular rationale for how the Rho ATPase domains distinguishes between distinct RNA sequences, and establish structural snapshots of substepping events in a hexameric helicase/translocase.

Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

The Golgi-localized Arabidopsis endomembrane protein12 contains both endoplasmic reticulum export and Golgi retention signals at its C terminus.

Endomembrane proteins (EMPs), belonging to the evolutionarily conserved transmembrane nine superfamily in yeast and mammalian cells, are characterized by the presence of a large lumenal N terminus, nine transmembrane domains, and a short cytoplasmic tail. The Arabidopsis thaliana genome contains 12 EMP members (EMP1 to EMP12), but little is known about their protein subcellular localization and function. Here, we studied the subcellular localization and targeting mechanism of EMP12 in Arabidopsis and demonstrated that (1) both endogenous EMP12 (detected by EMP12 antibodies) and green fluorescent protein (GFP)-EMP12 fusion localized to the Golgi apparatus in transgenic Arabidopsis plants; (2) GFP fusion at the C terminus of EMP12 caused mislocalization of EMP12-GFP to reach post-Golgi compartments and vacuoles for degradation in Arabidopsis cells; (3) the EMP12 cytoplasmic tail contained dual sorting signals (i.e., an endoplasmic reticulum export motif and a Golgi retention signal that interacted with COPII and COPI subunits, respectively); and (4) the Golgi retention motif of EMP12 retained several post-Golgi membrane proteins within the Golgi apparatus in gain-of-function analysis. These sorting signals are highly conserved in all plant EMP isoforms and, thus, likely represent a general mechanism for EMP targeting in plant cells.

Unique tri-output optical probe for specific and ultrasensitive detection of hydrazine.

An optical probe based on colorimetric and ratiometric as well as chemiluminometric signal outputs is developed for the specific detection of hydrazine. On the basis of a Gabriel-type reaction, hydrazinolysis of a simple probe CF (4-phtalamide-N-(4'-methylcoumarin) naphthalimide) produces both the fluorescence of 7-amino-4-methylcoumarin with the max emission wavelength changed from 480 to 420 nm (along with a color change from yellow to transparent) and the luminol chemiluminescence activated by H2O2 with a max emission wavelength at 450 nm. The experimental detection limit of hydrazine is 3.2 ppb (0.1 µM). Selectivity experiments proved CF has excellent selectivity to hydrazine over other interfering substances. Probe CF was also successfully applied in the vapor hydrazine detection over other interfering volatile analytes. Furthermore, the probe CF loaded thin-layer chromatography (TLC) plate for vapor hydrazine detection limit is 5.4 mg/m(3) which is well below the half lethal dose of hydrazine gas for mice (LC50(mice), 330 mg/m(3)) and National Institute of Occupational Safety and Health's immediately dangerous to life or health limit (NIOSHIDLH, 66 mg/m(3)). With H2O2, only hydrazinolysis product luminol can be lighted at 450 nm, other species have no signal. Probe CF can also be used for the detection of hydrazine in HeLa cells.

Cognitive function, mood, and sleep quality in patients treated with intensity-modulated radiation therapy for nasopharyngeal cancer: a prospective study.

OBJECTIVE: The aim of this study was to prospectively evaluate the cognitive function, depression, anxiety, and sleep quality in patients with nasopharyngeal cancer (NPC) before and after intensity-modulated radiotherapy (IMRT). METHODS: Eligible patients with newly diagnosed NPC treated with primary IMRT were recruited. A series of neuropsychological tests were performed within 1 week before and after IMRT. Cognitive function was measured with the Das-Naglieri cognitive assessment system. The Self-rating Anxiety Scale and Self-rating Depression Scale were used to assess mood states. Sleep quality was evaluated by means of the Pittsburgh Sleep Quality Index. RESULTS: A total of 51 patients were enrolled. The overall prevalence of depression, anxiety, and poor sleep quality showed a significant increase after RT, compared with their pre-RT levels (39.2% vs. 3.9%, p = 0.000; 19.6% vs. 3.9%, p = 0.039; 64.7% vs. 37.3%, p = 0.003, respectively). Multiple linear regression analysis revealed that pre-RT depression and younger age and pre-RT anxiety and younger age were significant predictors of post-RT depression and anxiety, respectively (p < 0.05). Poor sleep quality before treatment was also associated with poor sleep after RT (p = 0.032). However, the cognitive function evaluated by the cognitive assessment system from pre-RT was similar to the post-RT results. CONCLUSIONS: Exposure to ionizing radiation for the treatment of NPC decreased mood and sleep quality following IMRT, especially for patients with depression, anxiety, younger age, or poor sleep before treatment. No acute cognitive deficits were found resulting from IMRT, but the long-term effects of RT might still warrant concern.

Identification of patients with nasopharyngeal carcinoma by serum protein profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: As diagnosis of nasopharyngeal carcinoma at an early disease stage is important, we attempted to distinguish between patients with nasopharyngeal carcinoma and noncancer controls by using serum protein profiles. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and CM10 protein chip were used to detect the serum proteomic patterns of 65 patients with nasopharyngeal carcinoma before radiotherapy and 93 noncancer controls. Proteomic spectra of serum samples from 50 nasopharyngeal carcinoma patients and 60 noncancer controls were used as a training set. The validity of the classification tree was then challenged with a blind test set which included another 15 patients with nasopharyngeal carcinoma and 33 noncancer controls. Biomarker Wizard 3.01 and Biomarker Pattern 5.01 were used in combination to analyze the data and to develop diagnostic models. RESULTS: 21 protein peaks were significantly different between nasopharyngeal carcinoma and controls. 4 mass peaks (M4182, M5343, M5913 and M8702 mass/charge ratio) were chosen automatically to construct a classification tree. The classification tree correctly determined 93.8 % (45/48) of the test samples with 93.3 % (14/15) of the nasopharyngeal carcinoma samples and 93.9 % (31/33) of the noncancer samples. Using a combination of serum protein profiles and Epstein-Barr viral capsid antigen immunoglobulin A antibody tests, the diagnostic sensitivity and specificity were increased to 100 and 97 %, respectively. CONCLUSIONS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry could correctly distinguish nasopharyngeal carcinoma from noncancer individuals and showed great potential for the development of a screening test for the detection of nasopharyngeal carcinoma.

Sleep disturbance in Angelman syndrome patients.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression of the maternal ubiquitin protein ligase E3A gene (UBE3A). As one of the most challenging symptoms and important focuses of new treatment, sleep disturbance is reported to occur in 70-80% of patients with AS and has a serious impact on the lives of patients and their families. Although clinical studies and animal model studies have provided some clues, recent research into sleep disorders in the context of AS is still very limited. It is generally accepted that there is an interaction between neurodevelopment and sleep; however, there is no recognized mechanism for sleep disorders in AS patients. Accordingly, there are no aetiologically specific clinical treatments for AS-related sleep disorders. The most common approaches involve ameliorating symptoms through methods such as behavioural therapy and symptomatic pharmacotherapy. In recent years, preclinical and clinical studies on the targeted treatment of AS have emerged. Although precision therapy for restoring the UBE3A level and the function of its signalling pathways is inevitably hindered by many remaining obstacles, this approach has the potential to address AS-related sleep disturbance.

Nomogram model of survival prediction for nasopharyngeal carcinoma with lung metastasis: developed from the SEER database and validated externally.

Objective: Distant metastasis occurs in some patients at the first diagnosis of nasopharyngeal carcinoma (NPC), the prognosis is poor, and there are significant individual differences. This study established a nomogram model of lung metastasis of NPC as a supplement to TNM staging. Methods: The training cohort is used to build the nomogram model, and the validation cohort is used to evaluate the model. The training cohort of 177 patients is from the Surveillance, Epidemiology, and End Results (SEER) database. Factors affecting overall survival (OS) in patients with lung metastasis of NPC analysis by Cox regression analysis and then a nomogram were established. 122 patients from the Affiliated Tumor Hospital of Guangxi Medical University were selected as the external validation cohort. The concordance index (C-index), the area under the curve (AUC), and the calibration curve were used to assess the accuracy of the nomogram and used the decision curve analysis (DCA) curve to measure the clinical benefit capacity of the model. The patients were separated into two groups with different risks, and the "Kaplan-Meier (KM)" survival analysis was used to evaluate the differentiation ability of the model. Results: Age, T-stage, radiation, chemotherapy, and brain metastases can affect the OS in NPC with lung metastasis. A nomogram was developed according to the above five factors. The C-index of the training cohort and the validation cohort were 0.726 (95% CI: 0.692-0.760) and 0.762 (95% CI: 0.733-0.791). The AUC of the nomogram was better than that of the TNM staging. In the training cohort, the nomogram predicted OS AUC values of 0.767, 0.746, and 0.750 at 1, 2, and 3 years, TNM stage of 0.574, 0.596, and 0.640. In the validation cohort, nomogram predictions of OS AUC values of 0.817, 0.857, and 0.791 for 1, 2, and 3 years, TNM stage of 0.575, 0.612, and 0.663. DCA curves suggest that nomogram have better clinical net benefits than TNM staging. The KM survival analysis shows that the nomogram has a reasonable risk stratification ability. Conclusion: This study successfully established a nomogram model of NPC lung metastasis, which can be used as a supplement to TNM staging and provide reference for clinicians.