Tryptophan hydroxylase 1 drives glioma progression by modulating the serotonin/L1CAM/NF-κB signaling pathway.

BACKGROUND: Glioma is one of the main causes of cancer-related mortality worldwide and is associated with high heterogeneity. However, the key players determining the fate of glioma remain obscure. In the present study, we shed light on tumor metabolism and aimed to investigate the role of tryptophan hydroxylase 1 (TPH-1) in the advancement of glioma. METHOD: Herein, the levels of TPH-1 expression in glioma tissues were evaluated using The Cancer Genome Atlas (TCGA) database. Further, the proliferative characteristics and migration ability of TPH-1 overexpressing LN229/T98G cells were evaluated. Additionally, we performed a cytotoxicity analysis using temozolomide (TMZ) in these cells. We also examined the tumor growth and survival time in a mouse model of glioma treated with chemotherapeutic agents and a TPH-1 inhibitor. RESULTS: The results of both clinical and experimental data showed that excess TPH-1 expression resulted in sustained glioma progression and a dismal overall survival in these patients. Mechanistically, TPH-1 increased the production of serotonin in glioma cells. The elevated serotonin levels then augmented the NF-κB signaling pathway through the upregulation of the L1-cell adhesion molecule (L1CAM), thereby contributing to cellular proliferation, invasive migration, and drug resistance. In vivo experiments demonstrated potent antitumor effects, which benefited further from the synergistic combination of TMZ and LX-1031. CONCLUSION: Taken together, these data suggested that TPH-1 facilitated cellular proliferation, migration, and chemoresistance in glioma through the serotonin/L1CAM/NF-κB pathway. By demonstrating the link of amino acid metabolic enzymes with tumor development, our findings may provide a potentially viable target for therapeutic manipulation aimed at eradicating glioma.

Risk scores for predicting dysphagia in critically ill patients after cardiac surgery.

BACKGROUND: This study aimed at developing and validating a scoring model to stratify critically ill patients after cardiac surgery based on risk for dysphagia, a common but often neglected complication. METHODS: Data were prospectively collected and analyzed from January 2016 to June 2017 from 395 consecutive post cardiac surgery patients at the cardiac care unit (CCU) at a single center; 103 (26.1%) developed dysphagia. Univariate and multivariate logistic analyses were used to identify independent predictors for dysphagia. The survival nomogram was developed on the basis of a multivariable Cox model, which allowed us to obtain survival probability estimations. The predictive performance of the nomogram was verified for discrimination and calibration. Areas under receiver operating characteristic curve analysis were used to illustrate and evaluate the diagnostic performance of the novel model. RESULTS: The final novel scoring model, named SSG-OD, consists of three independent factors: gastric intubation (OR = 1.024, 95% CI 1.015-1.033), sedative drug use duration (OR = 1.031, 95% CI 1.001-1.063) and stroke or not (OR = 6.182, 95% CI 3.028-12.617). SSG-OD identified patients at risk for dysphagia with sensitivity of 68.5% and specificity of 89.0% (OR = 0.833, 95% CI: 0.782-0.884). The positive and negative likelihood ratios were 6.22 and 0.35. CONCLUSIONS: The novel SSG-OD scoring system to risk stratify CCU patients for dysphagia is an easy-to-use bedside prognostication aid with good predictive performance and the potential to reduce aspiration incidence and accelerate recovery.

Use of the cardiopulmonary coupling index based on refined composite multiscale entropy for prognostication of acute type A aortic dissection.

Objectives: The aim of this study is to assess the influence of cardiopulmonary coupling (CPC) based on RCMSE on the prediction of complications and death in patients with acute type A aortic dissection (ATAAD). Background: The cardiopulmonary system may be nonlinearly regulated, and its coupling relationship with postoperative risk stratification in ATAAD patients has not been studied. Methods: This study was a single-center, prospective cohort study (ChiCTR1800018319). We enrolled 39 patients with ATAAD. The outcomes were in-hospital complications and all-cause readmission or death at 2 years. Results: Of the 39 participants, 16 (41.0%) developed complications in the hospital, and 15 (38.5%) died or were readmitted to the hospital during the two-year follow-up. When CPC-RCMSE was used to predict in-hospital complications in ATAAD patients, the AUC was 0.853 (p < 0.001). When CPC-RCMSE was used to predict all-cause readmission or death at 2 years, the AUC was 0.731 (p < 0.05). After adjusting for age, sex, ventilator support (days), and special care time (days), CPC-RCMSE remained an independent predictor of in-hospital complications in patients with ATAAD [adjusted OR: 0.8 (95% CI, 0.68-0.94)]. Conclusion: CPC-RCMSE was an independent predictor of in-hospital complications and all-cause readmission or death in patients with ATAAD.

Bergaptol Alleviates LPS-Induced Neuroinflammation, Neurological Damage and Cognitive Impairment via Regulating the JAK2/STAT3/p65 Pathway.

Purpose: Neuroinflammation is considered a critical pathological process in various central nervous system (CNS) diseases and is closely related to neuronal death and dysfunction. Bergaptol is a natural 5-hydroxyfurocoumarin found in lemon, bergamot and other plants. Some studies have confirmed its anti-cancer, anti-inflammatory and anti-atherogenic functions, indicating that it may have significant medicinal value. In this study, we investigated the potential effect of Bergaptol in vitro and in vivo neuroinflammatory models. Methods: Mice were injected with LPS (40 µg/kg) into the hippocampal CA1 region and then injected intraperitoneally with Bergaptol (10, 20 and 40 mg/kg) once a day for two weeks. In addition, to verify the effect of Bergaptol on BV2 cells, Bergaptol with different concentrations (5, 10 and 20 µg/mL) was firstly incubated for 1 hour, then LPS with a concentration of 1 µg/mL was added and incubated for 23 hours. Results: Bergaptol treatment significantly improved the cognitive impairment induced by LPS. In addition, Bergaptol significantly inhibited the reduction of dendritic spines and the mRNA level of inflammatory factors (TNF-α, IL-6 and IL-1ß) in hippocampal induced by LPS. In vitro, Bergaptol inhibited the production of TNF-α, IL-6 and IL-1ß from LPS-treated BV-2 cells. In addition, Bergaptol treatment significantly reduced the phosphorylation levels of JAK2, STAT3 and p65 in LPS-stimulated BV-2 cells. Conclusion: In conclusion, our results suggest that Bergaptol alleviates LPS-induced neuroinflammation, neurological damage and cognitive impairment by regulating the JAK2/STAT3/P65 pathway, suggesting that Bergaptol is a promising neuroprotective agent.

Age shock index and age-modified shock index are strong predictors of outcomes in ST-segment elevation myocardial infarction patients undergoing emergency percutaneous coronary intervention.

BACKGROUND: Early identification of high-risk patients provides clinicians with greater decision-making time and better informs strategies to cope with disease. The predictive values of age shock index (age SI) and age-modified shock index (age MSI) in ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI) have rarely been reported, especially compared with those for SI, MSI, and the Global Registry of Acute Coronary Events (GRACE) risk score. PATIENTS AND METHODS: Nine hundred and eighty-three STEMI patients undergoing emergency PCI between January 2014 and September 2017 were analyzed in a retrospective cohort study. The primary outcomes were rates of in-hospital cardiovascular events, and 6-month and long-term all-cause mortality. RESULTS: In multivariate analyses, the predictive values of age SI and age MSI were comparable to that of the GRACE score, but superior to those of SI and MSI for in-hospital cardiac mortality [age SI: odds ratio (OR) = 1.05, P < 0.001, area under the receiver operating characteristic (ROC-AUC) = 0.805, P < 0.001; age MSI: OR = 1.04, P < 0.001, ROC-AUC = 0.813, P < 0.001; GRACE score: OR = 1.03, P < 0.001, ROC-AUC = 0.827, P < 0.001], 6-month all-cause mortality (age SI: OR = 1.04, P < 0.001, ROC-AUC = 0.791, P < 0.001; age MSI: OR = 1.03, P < 0.001, ROC-AUC = 0.801, P < 0.001; GRACE score: ROC-AUC = 0.828, P < 0.001), long-term all-cause mortality [age SI: hazard ratio (HR) = 1.06, P < 0.001, ROC-AUC = 0.798, P < 0.001; age MSI: HR = 1.04, P < 0.001, ROC-AUC = 0.84, P < 0.001; GRACE score: ROC-AUC = 0.822, P < 0.001] and post-discharge all-cause mortality (age SI: HR = 1.05, P < 0.001, ROC-AUC = 0.78, P = 0.001; age MSI: HR = 1.05, P < 0.001, ROC-AUC = 0.789, P < 0.001; GRACE score: ROC-AUC = 0.812, P < 0.001). CONCLUSION: Age SI and age MSI are stronger predictors than SI and MSI for in-hospital cardiovascular events, and 6-month and long-term all-cause mortality in STEMI patients undergoing emergency PCI. Age SI and age MSI appear to be convenient and simpler indicators than the GRACE score.

Association between admission lactate levels and mortality in patients with acute coronary syndrome: a retrospective cohort study.

OBJECTIVE: Hyperlactatemia at admission is associated with poor outcome in critically ill patients. However, data on the prognostic value of blood lactate level in patients with acute coronary syndrome (ACS) are limited. The present study assessed the prognostic effect of admission lactate level in a large population of patients with ACS. MATERIALS AND METHODS: This was a retrospective observational study including patients with ACS who were admitted to the Coronary Care Unit of the First Affiliated Hospital of Wenzhou Medical University between 2014 and 2017. Patients were divided into tertiles of lactate level (T1: <1.8; T2: 1.8-2.6; T3: ≥2.7 mmol/l). The clinical outcomes were 30-day and 180-day mortality from hospital admission. Cox proportional hazards models were used to evaluate the association between lactate level and survival. RESULTS: A total of 1865 consecutive patients with ACS were enrolled. Significant positive associations were observed between admission lactate level and both 180-day and 30-day mortality, with highest risk for lactate greater than or equal to 2.7 mmol/l. The adjusted hazard ratio for 180-day mortality was 2.09 [95% confidence interval (CI): 1.18-3.71, P=0.011] for T3 and 1.53 (95% CI: 0.86-2.72, P=0.147) for T2 compared with T1 (P for trend=0.006), and 1.10 (95% CI: 1.02-1.18, P=0.010) for each unit increase in lactate level. Similar trends were observed for 30-day mortality. The association was highly consistent across all subgroups studied (all P for interaction >0.05). CONCLUSION: In patients with ACS, elevated admission lactate level is an independent predictor of 30-day and 180-day all-cause mortality.

The effect of night shift on sleep quality and depressive symptoms among Chinese nurses.

PURPOSE: Night shift is associated with adverse physical and psychological health outcomes such as poor sleep quality and depressive symptoms. We aimed to compare sleep quality as well as depressive symptoms in nurses working night shifts to those working day shifts only and explore the association between sleep quality and depressive symptoms among nurses. PATIENTS AND METHODS: Eight hundred sixty-five nurses were enrolled in the current study. Sleep quality and depressive symptoms among nurses were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depressive Disorders Rating Scale (HADS), respectively. RESULTS: PSQI and HADS scores were both significantly higher in the nurses working night shifts (P<0.05) than in those working day shifts only. Besides, there was a positive correlation between PSQI and HADS scores. Binary logistic regression showed that night shift and poor sleep quality were independent risk factors of depressive symptoms among nurses. CONCLUSION: Higher rates of depression among Chinese nurses working night shifts may be associated with poor sleep quality induced by night shift.

Continuous renal replacement therapy for haemodynamic collapse and rhabdomyolysis induced by pheochromocytoma crisis.

Pheochromocytoma associated with pregnancy is not common. Caesarean section may induce pheochromocytoma crisis, resulting in a lethal condition. The clinical picture of pheochromocytoma crisis is extremely variable. In this report, we describe a case of severe pheochromocytoma crisis induced by caesarean section presenting with hyperpyrexia, haemodynamic collapse, muscle weakness, heart failure, and acute kidney injury. Furthermore, we report that the muscle weakness was a manifestation of rhabdomyolysis, resulting from the pheochromocytoma crisis. Standard medical therapy failed to halt the patient's rapidly deteriorating condition. Continuous renal replacement therapy removed catecholamines from the circulation, resulting in improvement of haemodynamics and abrogation of rhabdomyolysis.