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Background Treatment of nasopharyngeal carcinoma (NPC) is evolving toward Intensity-modulated radiotherapy (IMRT) era, which requires patient-specific reestimation of survival outcomes in modern health care. Methods A total of 488 detectable pre-treatment Epstein-Barr virus (EBV) DNA patients (stage II-IVa) treated with induction chemotherapy (IC) and IMRT were examined (training set, n = 325; validation set, n = 163). Results Concurrent chemotherapy (CC) was still an independent prognosticator for overall survival (OS) and progression-free survival (PFS). Both nomograms included age, T classification, N classification, post-IC EBV DNA, and CC. Predictions correlated well with observed 3-/5-year OS and PFS. The concordance index was 0.776 (95% confidence interval (CI) 0.69-0.86) for OS and 0.742 (95% CI 0.65-0.83) for PFS in the validation cohort. The nomograms can successfully classify patients into low- and high-risk groups. Conclusion The validated nomograms provided useful prediction of OS and PFS for detectable pre-treatment EBV DNA patients with NPC in IMRT era.

Objective Nalbuphine and dexmedetomidine are both used as anesthesia adjuvants for brachial plexus block, but their efficacy and safety in younger patients are not clear. In this study, we aimed to compare the efficacy and side effects of these 2 drugs in young patients undergoing brachial plexus block. Methods We recruited 48 young patients aged 18 to 30 years requiring supraclavicular brachial plexus block. Subjects were randomly divided into 2 groups. Patients in group levobupivacaine+nalbuphine received 28 mL of 0.5% levobupivacaine and 10 mg of nalbuphine diluted in 2 mL 0.9% saline. Patients in group levobupivacaine+dexmedetomidine (LD) received 28 mL of 0.5% levobupivacaine and 0.75 μg/kg dexmedetomidine diluted in 2 mL 0.9% saline. Demographic information, types of fracture, onset time of motor and sensory blocks, duration of block, side effects, and analgesic use were recorded. Results We found that the 2 groups did not differ significantly in the demographic profile and fracture type. Compared with group LD, group LD had significantly shorter sensory and motor block onset time, longer block duration, less analgesic need, and less side effects. Conclusion In summary, our study suggests that nalbuphine is a better anesthesia adjuvant for supraclavicular brachial plexus block in young patients.

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.

Introduction: Ketamine, which is widely used in anesthesia, can induce cortical neurotoxicity in patients. This study aims to investigate the effects of long non-coding RNA (lncRNA) LINC00641 on the ketamine-induced neural injury. Materials and Methods: In this study, rat brain embryonic stem cell (ESC)-derived neurons were used as a cell model and Sprague–Dawley postnatal day 7 rat 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 csapase-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. Results: Ketamine induced the apoptosis of ESC-derived neurons, accompanied with down-regulation of LINC00641 and BDNF, and up-regulation of miR-497-5p. LINC00641 overexpression enhanced the resistance to the apoptosis of ESC-derived neurons, 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. Conclusion: Collectively, LINC00641/miR-497-5p/BDNF axis was validated to be an important signaling pathway in modulating ketamine-induced neural injury.

Background: Previous studies have shown that survivin has potential prognostic value in nasopharyngeal carcinoma. However, the results remained controversial until now. Thus, to investigate the influence of survivin expression on prognosis and clinical characteristics in nasopharyngeal carcinoma, we performed this meta-analysis. Methods: We searched PubMed, PMC, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure electronic databases from their establishment to 1 March 2021. The pooled hazard ratio (HR) and the pooled odds ratio (OR) were used to evaluate the prognostic and clinicopathological values of survivin in nasopharyngeal carcinoma. We used the I2 statistic and the Q test to evaluate heterogeneity. Meta-regression, publication bias, and sensitivity analyses were also conducted. Results: A total of 26 eligible studies with 2278 patients were included in our meta-analysis. We found that the expression of survivin is connected with poor overall survival (HR=1.94; 95% confidence interval (CI)=1.52-2.48; P

Dexmedetomidine is a local anesthetic adjuvant that exerts neuroprotective effects in addition to its sedative and analgesic properties. However, it is not clear whether dexmedetomidine causes any neurotoxicity in neonates. We injected dexmedetomidine alone or in combination with ropivacaine to induce brachial plexus block in rats of different age, corresponding to human neonate, childhood, adolescence and adulthood. We then examined pro-inflammatory cytokines and activated caspase 3 to determine the neurotoxicity effects. We found that high dose of dexmedetomidine significantly reduced IL-6 and TNF-α levels in all aged rat brachial plexus compared to saline treatment, and these levels are similar to that of control brachial plexus at postnatal day 14, 18 and adulthood. Caspase 3 level is not significantly different between dexmedetomidine and control group, except that it is higher in dexmedetomidine treated group at postnatal day 5. We found that this neurotoxicity effect of dexmedetomidine is only present at a high dose. Dexmedetomidine shows minimal neurotoxicity in neonate rats during brachial plexus block when moderate doses are administered. This observation warrants more detailed clinical studies to determine the safety of using dexmedetomidine for brachial plexus block in infant or early childhood patients.

Background: Over the past 5 years, many studies have reported the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1α) in nasopharyngeal carcinoma. However, the results have not reached a consensus until now. Therefore, we performed this meta-analysis to investigate the influence of HIF-1α expression on the prognosis and clinical characteristics in nasopharyngeal carcinoma. Methods: We searched PubMed, the Cochrane Library, Embase (via Ovid interface), Web of Science, and China National Knowledge Infrastructure electronic databases from their establishment to 6 December 2017. We calculated the hazard ratio (HR) and the odds ratio (OR) to assess the prognostic and clinicopathological values of HIF-1α, respectively. Q test and I2 statistic were applied to evaluate heterogeneity. We also conducted publication bias and sensitivity analyses. Results: A total of 18 studies with 1476 patients were included in our meta-analysis. We found HIF-1α expression was associated with poor overall survival (HR=1.77; 95% confidence interval (CI) 1.35, 2.32; PConclusions: Our study demonstrated that HIF-1α could be an appropriate prognostic biomarker for nasopharyngeal carcinoma patients.

Purpose of the research Post operational cognitive dysfunction (POCD) occurs in patients after anesthesia and surgery. Abnormal histone acetylation and neuroinflammation are key factors in the pathogenesis of cognitive impairment. Apigenin not only has an anti-inflammatory activity but also modifies histone acetylation. We aimed to investigate whether apigenin can attenuate isoflurane exposure-induced cognitive decline by regulating histone acetylation and inflammatory signaling. Materials and methods Spatial learning and memory were assessed by Morris water maze test. Levels of histone acetylation, BDNF and downstream signaling, and inflammatory components were analyzed. Principal results Isoflurane exposure in aged rats lead to impaired spatial learning and memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation, which was accompanied by reduced BDNF expression and suppressed BDNF downstream signaling pathway. Apigenin restored histone acetylation and BDNF signaling. Apigenin also suppressed isoflurane exposure induced upregulation of proinflammatory cytokines and NFκB signaling pathway. Major conclusions Memory impairment induced by isoflurane exposure is associated with dysregulated histone acetylation in the hippocampus, which affects BDNF expression and hence BDNF downstream signaling pathway. Apigenin recovers cognitive function by restoring histone acetylation and suppressing neuroinflammation.

To develop a multidimensional nomogram for predicting the progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) (stage III-IVa).A total of 224 patients with locoregionally advanced NPC (training cohort, n = 149; validation cohort, n = 75) were retrospectively included. We extracted 260 radiomic features from the primary tumor and lymph nodes on the axial contrast-enhanced T1 weighted and T2 weighted MRI. Radiomic signatures of the gross tumor volume (RSnx) and lymph node (RSnd), Dose Volume Histogram (DVH) signature reflecting planning score (PS), and clinical characteristics were included as potential predictors of PFS. The least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and data dimension reduction. A nomogram was developed by incorporating the selected predictors. The C-index and calibration curve were used to assess discrimination and calibration power of the nomogram, respectively.RSnd, PS, and tumor-node-metastasis (TNM) stage were the independent predictors for PFS (all p 0.05). The nomogram integrating the three factors achieved a C-index of 0.811 (95% CI: 0.74-0.882) in the validation cohort for predicting PFS, which outperformed than that of the TNM stage alone (C-index, 0.613, 95% CI: 0.532-0.694). Subgroup analysis showed Epstein-Barr virus (EBV) DNA status improved the predictive accuracy of the nomogram (C-index, 0.86, 95% CI: 0.787-0.933).The multidimensional nomogram incorporating RSnd, PS, and TNM stage showed high performance for predicting PFS in patients with locoregionally advanced NPC.

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.

Hydromorphone has been shown to play protective effect in rat glial cell. However, whether hydromorphone plays important roles in ischemia–reperfusion (IR) injury and the involved signaling pathway remains unclear. In this study, we detected whether HM plays protective effect in IR injury mouse model, further followed by the mechanism exploration. Preconditioning with hydromorphone was performed for continuous 4 days at the doe of 2 mg/kg before IR injury induction. Intraperitoneal injection of rapamycin (Rapa) was administrated to examine the role of mTOR in IR injury. The mRNA expression level was detected by RT-PCR, and protein expression level was detected by western blot. Latency time and apoptosis of hippocampal CA1 neurons were detected 72 h after IR injury induction. Preconditioning with hydromorphone significantly increased Latency time, decreased apoptosis of hippocampal CA1 neurons and suppressed IR induced oxidative stress. Mechanically, preconditioning with hydromorphone increased Bcl-2 and p-mTOR expression levels and decreased Bax expression levels. Rapa administration reverses the role of hydromorphone in protecting hippocampal CA1 neurons from IR injury. Hydromorphone protect hippocampal CA1 neurons from IR injury via activating mTOR signaling pathway.