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Abstract Nasopharyngeal carcinoma (NPC) is the most common cancer originating in nasopharynx. Metabolic reprogramming plays a critical role in tumor progression. Exploring mechanisms underlying metabolic reprogramming contributes to deeper understanding of NPC pathogenesis. Here, we found downregulation of RORA and SPLUNC1 in NPC, and RORA downregulation indicates poor prognosis. RORA binds to SPLUNC1 promoter to induce its transcription, and RORA overexpression inhibits cell proliferation and glycolysis by directly upregulating SPLUNC1. UBR5 inhibits RORA via promoting RORA ubiquitination and degradation, and UBR5 silencing represses proliferation and glycolysis in NPC. Additionally, METTL14, which is highly expressed in NPC, facilitates UBR5 mRNA stability by promoting its m6A modification through IGF2BP2. UBR5/RORA/SPLUNC1 axis facilitates M2 polarization by activating the GPR132 signaling. UBR5 silencing inhibits tumor growth, glycolysis and M2 polarization through RORA/SPLUNC1 signaling in mice. In conclusion, UBR5 promotes proliferation, glycolysis and M2 polarization by metabolically reprograming NPC cells through suppression of the RORA/SPLUNC1 signaling.

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.

Background: Nursing home is critical for the elderly. Methods: To investigate the effects of decision-making process in terms of choosing room type and roommates on cognitive and psychosocial conditions of the elderly, 174 eligible participants were randomly assigned into three groups. In the first two groups, participants were randomly assigned to single-person rooms (Group SPR, n = 58) and multi-person rooms (2–4 persons per room, Group MPR, n = 58), and the third group of participants were allowed to voluntarily choose to live in single-person room or with preferred roommates (Group VPR, n = 58). Results: Participants who voluntarily choose room type and roommates (Group VPR) showed the least deterioration of cognitive function, psychosocial, and physical health, with Group MPR showing less deterioration than Group SPR. Allowing elderly people to voluntarily choose room type and roommate is better for preserving their cognitive, psychological, and physical health. Conclusions: Voluntary choice of room type and roommates is beneficial to the cognitive, psychological, and physical health of elderly people.

Background: Mindfulness training exhibits favorable effects on both psychological and physiological outcomes. We aimed at assessing its effects on post-percutaneous coronary intervention (PCI) patients. Methods: We recruited 357 patients arranged with PCI and randomized them in a ratio of 1:1 (n = 178 versus n = 179) into a 3-month mindfulness training class in addition to usual care. The primary outcomes were the physiological and health-related quality of life outcomes of patients post-PCI. The secondary outcomes were the psychological outcomes of the patients. Results: Compared to the control group, the 3-month mindfulness training improved the physiological outcomes including systolic blood pressure, body mass index, total cholesterol level, low-density lipoprotein-cholesterol, and triglyceride levels of patients post-PCI. The psychological outcomes including depression, anxiety, self-efficacy, and stress of these patients were also improved statistically. Conclusion: Mindfulness training exhibited benefits on both physiological and psychological outcomes of patients post-PCI.

Background: Apigenin has been reported to exhibit anti-inflammatory and anti-oxidative activities. This study aimed to investigate the protective role of Apigenin on chemotherapy-induced peripheral neuropathy (CIPN). Methods: CIPN mouse model was established using Paclitaxel treatment. Hot plate and tail prick latency tests were performed to examine the allodynia and hyperalgesia behaviors. Anti-inflammatory and anti-oxidative effects of Apigenin on CIPN were determined by enzyme-linked immunosorbent (ELISA) assay, Western blot, and qRT-PCR. Nuclear recruitment of nuclear factor erythroid 2-related factor 2 (NRF2) was analyzed to evaluate the underlying mechanisms of the protective effects of Apigenin. Results: Apigenin significantly alleviated CIPN-induced nociceptive behaviors of CIPN mice. It also decreased the TNF-α and IL-1β levels, suppressed oxidative stress and inflammation in the surgical spinal cord tissues. Mechanistically, Apigenin altered the pro-inflammatory and anti-inflammatory phenotypes ratio of microglia through promoting the nuclear recruitment of NRF2 and activating the NRF2/Antioxidant Response Element (ARE) signaling pathway. Conclusions: In summary, Apigenin relieves CIPN by regulating microglia activation and polarization, which provides a potential therapeutic strategy for CIPN treatment.

BackgroundThe efficiency of concurrent chemotherapy (CC) remains controversial for stage II–IVa nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT). Therefore, we aimed to propose a nomogram to identify patients who would benefit from CC.MethodsA total of 434 NPC patients (stage II–IVa) treated with IC followed by IMRT between January 2010 and December 2015 were included. There were 808 dosimetric parameters extracted by the in-house script for each patient. A dosimetric signature was developed with the least absolute shrinkage and selection operator algorithm. A nomogram was built by incorporating clinical factors and dosimetric signature using Cox regression to predict recurrence-free survival (RFS). The C-index was used to evaluate the performance of the nomogram. The patients were stratified into low- and high-risk recurrence according to the optimal cutoff of risk score.ResultsThe nomogram incorporating age, TNM stage, and dosimetric signature yielded a C-index of 0.719 (95% confidence interval, 0.658–0.78). In the low-risk group, CC was associated with a 9.4% increase of 5-year locoregional RFS and an 8.8% increase of 5-year overall survival (OS), whereas it was not significantly associated with an improvement of locoregional RFS (LRFS) and OS in the high-risk group. However, in the high-risk group, patients could benefit from adjuvant chemotherapy (AC) by improving 33.6% of the 5-year LRFS.ConclusionsThe nomogram performed an individualized risk quantification of RFS in patients with stage II–IVa NPC treated with IC followed by IMRT. Patients with low risk could benefit from CC, whereas patients with high risk may require additional AC.

BackgroundThe purpose of this retrospective analysis was to build and validate nomograms to predict the cancer-specific survival (CSS) and overall survival (OS) of head and neck neuroendocrine carcinoma (HNNEC) patients.MethodsA total of 493 HNNEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and 74 HNNEC patients were collected from the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital (HCH) between 2008 and 2020. Patients from SEER were randomly assigned into training (N=345) and internal validation (N=148) groups, and the independent data group (N=74) from HCH was used for external validation. Independent prognostic factors were collected using an input method in a Cox regression model, and they were then included in nomograms to predict 3‐, 5‐, and 10‐year CSS and OS rates of HNNEC patients. Finally, we evaluated the internal and external validity of the nomograms using the consistency index, while assessing their prediction accuracy using calibration curves. A receiver operating curve (ROC) was also used to measure the performance of the survival models.ResultsThe 3-, 5-, and 10-year nomograms of this analysis demonstrated that M classification had the largest influence on CSS and OS of HNNEC, followed by the AJCC stage, N stage, age at diagnosis, sex/gender, radiation therapy, and marital status. The training validation C-indexes for the CSS and OS models were 0.739 and 0.713, respectively. Those for the internal validation group were 0.726 and 0.703, respectively, and for the external validation group were 0.765 and 0.709, respectively. The area under the ROC curve (AUC) of 3-, 5-, and 10-year CSS and OS models were 0.81, 0.82, 0.82, and 0.78, 0.81, and 0.82, respectively. The C-indexes were all higher than 0.7, indicating the high accuracy ability of our model’s survival prediction.ConclusionsIn this study, prognosis nomograms in HNNEC patients were constructed to predict CSS and OS for the first time. Clinicians can identify patients’ survival risk better and help patients understand their survival prognosis for the next 3, 5, and 10 years more clearly by using these nomograms.

IntroductionKetamine, which is widely used in anesthesia, can induce cortical neurotoxicity in patients. This study aims to investigate the effects of long non-coding RNA LINC00641 on the ketamine-induced neural injury.Materials and MethodsIn this study, rat pheochromocytoma cells (PC12 cells) were used as a cell model and Sprague–Dawley postnatal day 7 rats were used for experiments in vivo. Ketamine-induced aberrant expression levels of LINC00641, miR-497-5p and brain-derived neurotrophic factor (BDNF) were examined by qRT-PCR. The effects of LINC00641 and miR-497-5p on ketamine-induced neural injury were then examined by MTT assays and TUNEL analysis. In addition, the activity of ROS and caspase-3 was measured. The regulatory relationships between LINC00641 and miR-497-5p, miR-497-5p and BDNF were detected by dual-luciferase reporter assay, respectively.ResultsKetamine induced the apoptosis of PC12 cells, accompanied by down-regulation of LINC00641 and BDNF, and up-regulation of miR-497-5p. LINC00641 overexpression enhanced the resistance to the apoptosis of PC12 cells, while transfection of miR-497-5p had opposite effects. Furthermore, LINC00641 could bind to miR-497-5p and reduce its expression, but indirectly increase the BDNF expression, which was considered as a protective factor in neural injury and activated TrkB/PI3K/Akt pathway.ConclusionCollectively, LINC00641/miR-497-5p/BDNF axis was validated to be an important signaling pathway in modulating ketamine-induced neural injury.

Cytokeratin fraction 21-1 (CYFRA 21-1) has been widely studied as an important biomarker in non-small cell lung cancer for both diagnosis and prognosis. Many studies have also assessed the clinical applications of CYFRA 21-1 in head and neck cancer, but the diagnostic and prognostic values of CYFRA 21-1 are not yet fully established. This pooled analysis aims at evaluating the diagnostic accuracy and prognostic applications of CYFRA 21-1 in patients with head and neck cancer. A systematic retrieval of literatures was conducted without time or language restrictions by searching PubMed, EMBASE, Web of Science, Cochrane library and China National Knowledge Infrastructure. Twenty studies were eligible for systematic review, of which 14 conformed for diagnostic analysis and 7 for prognostic analysis. The pooled sensitivity and specificity of CYFRA 21-1 analysis were 0.53 (95% CI: 0.39-0.67) and 0.97 (95% CI: 0.93-0.99), respectively. A high level of CYFRA 21-1 was significantly correlated with shorter overall survival (HR 1.33, 95% CI: 1.13-1.56) and disease-free survival (HR 1.48; 95%CI: 1.10-1.97). Current evidence indicates that the level of CYFRA 21-1 in the serum could be used as an indicator for monitoring tumor status and evaluating its curative effects.

Sevoflurane is an inhalation anaesthetic agent widely used in clinical settings. Despite good surgical outcomes using sevoflurane, patients frequently develop postoperative cognitive dysfunction (POCD). An enriched environment (EE), as a rehabilitation technique, could provide objects and tools to facilitate neuromotor and visual stimuli and brain activity, and is reported to improve cognitive functions. We aim to investigate the impairments of sevoflurane inhalation on cognitive function in mice and determine the benefits of EE in ameliorating POCD. Eighteen-month-old mice were exposed to sevoflurane inhalation for 2 h and then placed in standard environment (SE) or EE cages. The mice without sevoflurane exposure in standard or EE cages were used as controls. The behavioural tests include Morris water maze, Y maze and novel object recognition. Magnetic resonance imaging (MRI) was used to determine the blood circulation in the brains. The proangiogenic factors (CD31, angiopoietin-1, vascular endothelial growth factor, and N-cadherin) and neurotrophic (brain-derived neurotrophic factor, post-synaptic density protein 95) expression in hippocampus of aged mice were evaluated by Western blotting and RT-PCR analysis. Sevoflurane-exposed mice demonstrated reduced performance in learning, memory and spatial memory tests. Enriched environment improved the behavioural performance of sevoflurane-exposed animals. Sevoflurane exposure reduced the blood flow in the brains, and these effects were ameliorated by EE habitation. The EE also promoted the expression of angiogenic and neurotropic factors in sevoflurane-exposed animals. In summary, EE is effective in ameliorating the side-effects of sevoflurane exposure in aged mice. [ABSTRACT FROM AUTHOR]

To examine the effect and mechanism of dexmedetomidine pretreatment mediated adenylate adenosine monophosphate-activated protein kinase pathway on hypoxic reoxygenation injured rat cardiomyocytes. A total of sixty Sprague-Dawley rats were allocated into three groups, namely the sham surgery group, model group, and dexmedetomidine intervention group, utilizing a random number table. Each group consisted of twenty rats. The model group and the intervention group of dexmedetomidine were used to prepare a rat myocardial hypoxia reoxygenation injury model using an improved thread occlusion method. The sham surgery group only underwent thoracotomy without ligation, and the intervention group of dexmedetomidine was pretreated with dexmedetomidine before establishing the model. Western blot was used to detect adenosine monophosphate-activated protein kinase, uncoupling protein 2, and Kruppel-like factor 2 proteins; using flow cytometry to detect the average fluorescence intensity of reactive oxygen species; detection of cell apoptosis rate using terminal deoxynucleotidyl transferase dUTP nick end labeling method; using the enzyme-linked immunosorbent assay detection kit manual to detect serum interleukin-6 and tumor necrosis factor-alpha, interleukin-1 beta and the levels of various indicators such as superoxide dismutase and malondialdehyde. Adenosine monophosphate-activated protein kinase, Kruppel-like factor 2, and uncoupling protein 2 proteins in the myocardium of the model group rats were markedly lower than those of the sham operation group; adenosine monophosphate-activated protein kinase, Kruppel-like factor 2, and uncoupling protein 2 in the myocardium of rats in the dexmedetomidine intervention group were markedly higher than the model group. The superoxide dismutase level of the model group rats was markedly reduced than the sham operation group, with malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, interleukin-1 beta was markedly higher than that of the sham surgery group; superoxide dismutase, malondialdehyde, interleukin-6 and tumor necrosis factor-alpha in the intervention group of dexmedetomidine were markedly higher than the model group, tumor necrosis factor-alpha, interleukin-1 beta was markedly reduced than that of the model group. Dexmedetomidine can activate adenosine monophosphate-activated protein kinase pathway, upregulation of uncoupling protein 2 expressions and the inhibition of mitochondrial reactive oxygen species production are observed, thereby restraining the oxidative irritability of myocardial tissue under hypoxia/reoxygenation conditions and playing a role in myocardial cytoprotection. [ABSTRACT FROM AUTHOR]