Maribellus mangrovi sp. nov., an iron-reducing bacterium isolated from mangrove sediment.

A novel facultatively anaerobic and Gram-stain-negative bacterium, designated FJH33T, was isolated from mangrove sediment sampled in Zhangzhou, PR China. Cells of strain FJH33T were rod-shaped or slightly curved-shaped, with widths of 0.3-0.5 µm and lengths of 1.0-3.0 µm. Optimum growth of strain FJH33T occurred in the presence of 3 % NaCl (w/v), at 33 °C and at pH 7.0. Oxidase activity was negative, while catalase activity was positive. Its iron-reducing ability was determined. Based on 16S rRNA gene sequence similarity, strain FJH33T was most closely related to Maribellus luteus XSD2T (95.1 %), followed by Maribellus sediminis Y2-1-60T (95.0 %) and Maribellus maritimus 5E3T (94.9 %). Genome analysis of strains FJH33T and M. luteus XSD2T revealed low genome relatedness, with an average nucleotide identity value of 73.8% and a digital DNA-DNA hybridization value of 19.0%. Phylogenetic trees built from 16S rRNA genes and genome sequences showed that strain FJH33T represents a relatively independent phylogenetic lineage within the genus Maribellus. The major cellular fatty acids (≥10 %) were iso-C15 : 0 and C18 : 1 ω9c. The sole respiratory quinone was MK-7. The polar lipids consisted of phosphatidylethanolamine, diphosphatidylcholine, diphosphatidyglycerol and one unidentified lipid. The DNA G+C content was 41.4 mol%. Based on the integrated results of phylogenetic, physiological, biochemical and chemotaxonomic characterizations, we propose that strain FJH33T represents a novel species of the genus Maribellus, for which the name Maribellus mangrovi sp. nov. is proposed. The type strain is FJH33T (=KCTC 102210T=MCCC 1H01459T).

MRI-based radiomics feature combined with tumor markers to predict TN staging of rectal cancer.

The aim of this study is to evaluate the predictive ability of MRI-based radiomics combined with tumor markers for TN staging in patients with rectal cancer and to develop a prediction model for TN staging. A total of 190 patients with rectal adenocarcinoma who underwent total mesorectal excision at the First Affiliated Hospital of the Air Force Medical University between January 2016 and December 2020 were included in the study. An additional 54 patients from a prospective validation cohort were included between August 2022 and August 2023. Preoperative tumor markers and MRI imaging data were collected from all enrolled patients. The 190 patients were divided into a training cohort (n = 133) and a validation cohort (n = 57). Radiomics features were extracted by outlining the region of interest (ROI) on T2WI sequence images. Feature selection and radiomics score (Rad-score) construction were performed using least absolute shrinkage and selection operator regression analysis (LASSO). The postoperative pathology TNM stage was used to differentiate locally advanced rectal cancer (T3/4 or N1/2) from locally early rectal cancer (T1/2, N0). Logistic regression was used to construct separate prediction models for T stage and N stage. The models' predictive performance was evaluated using DCA curves and calibration curves. The T staging model showed that Rad-score, based on 8 radiomics features, was an independent predictor of T staging. When combined with CEA, tumor diameter, mesoretal fascia (MRF), and extramural venous invasion (EMVI), it effectively differentiated between T1/2 and T3/4 stage rectal cancers in the training cohort (AUC 0.87 [95% CI: 0.81-0.93]). The N-staging model found that Rad-score, based on 10 radiomics features, was an independent predictor of N-staging. When combined with CA19.9, degree of differentiation, and EMVI, it effectively differentiated between N0 and N1/2 stage rectal cancers. The training cohort had an AUC of 0.84 (95% CI: 0.77-0.91). The calibration curves demonstrated good precision between the predicted and actual results. The DCA curves indicated that both sets of predictive models could provide net clinical benefits for diagnosis. MRI-based radiomics features are independent predictors of T staging and N staging. When combined with tumor markers, they have good predictive efficacy for TN staging of rectal cancer.

Techno-functional properties of active film based on guar gum-propolis and its application for "Nanguo" pears preservation.

Guar gum (GG) composite films, incorporating the ethanolic extract of propolis (EEP), were prepared and subjected to a comprehensive investigation of their functional characteristics. The addition of EEP resulted in a discernible enhancement in the opacity, moisture barrier capacity, and elongation at break. Incorporating EEP led to a noteworthy increase in the total phenolic and total flavonoid content of the films, resulting in superior antioxidant capacity upon GG-EEP films. Remarkably, the addition of 5 % EEP yielded noteworthy outcomes, manifesting in a DPPH radical scavenging rate of 47.60 % and the ABTS radical scavenging rate of 94.87 %, as well as FRAP and cupric reducing power of 331.98 mmol FeSO4-7H2O kg-1 and 56.95 µg TE mg-1, respectively. In addition, GG-EEP films demonstrated antifungal effect against Penicillium expansum and Aspergillus niger, along with a sustained antibacterial effect against Escherichia coli and Staphylococcus aureus. GG-EEP films had superior inhibitory ability against Gram-positive bacteria than Gram-negative bacteria. Crucially, GG-EEP composite films played a pivotal role in reducing both lesion diameter and depth, concurrently mitigating weight loss and firmness decline during the storage period of "Nanguo" pears. Therefore, GG-EEP composite films have the considerable potential to serve as advanced and effective active packaging materials for food preservation.

Construction of a novel microRNA-based signature for predicting the prognosis of glioma.

Background and purpose: Glioma is a frequent primary brain tumor. MicroRNAs (miRNA) have been shown to potentially play a crucial part in tumor development. Based on miRNAs and clinical factors, a model was constructed to predict the glioma prognosis. Methods: The miRNA expression profiles of glioma come from The Cancer Genome Atlas (TCGA, training group) and Chinese Glioma Genome Atlas (CGGA, validation group). Regression analyses of Cox and Lasso were applied to identity miRNAs associated with glioma prognosis in the TCGA database. The miRNAs were combined with clinical factors to construct individualized prognostic prediction models, whose performance was validated in the CGGA database. The role of miRNA in glioma development was investigated by in vitro experiments.Results: We identified five key miRNAs associated with glioma prognosis and constructed a prediction model. The area under ROC curve for predicting 3-year survival of glioma patients in the TCGA and CGGA groups was 0.844 and 0.770, respectively. The nomogram constructed using the miRNA risk scores and clinical factors showed high accuracy of prediction in the TCGA group (C-index of 0.820) and the CGGA group (C-index of 0.722). The miR-196b-5p altered the migration, proliferation, invasion, and apoptosis of glioma cells by regulating target genes, according to in vitro experiments.Conclusions: A miRNA-based individualized prognostic prediction model was constructed for glioma and miR-196b-5p was identified as a potential biomarker of glioma development.

Repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy treatment in alcohol-dependent patients: A randomized, double-blind sham-controlled multicenter clinical trial.

Background: Alcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD. Materials and methods: A total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse. Results: The sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan-Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05). Conclusion: This study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

Socioeconomic status, individual behaviors and risk for mental disorders: A Mendelian randomization study.

BACKGROUND: There is increasing attention on the association of socioeconomic status and individual behaviors (SES/IB) with mental health. However, the impacts of SES/IB on mental disorders are still unclear. To provide evidence for establishing feasible strategies on disease screening and prevention, we implemented Mendelian randomization (MR) design to appraise causality between SES/IB and mental disorders. METHODS: We conducted a two-sample MR study to assess the causal effects of SES and IB (dietary habits, habitual physical activity, smoking behaviors, drinking behaviors, sleeping behaviors, leisure sedentary behaviors, risky behaviors, and reproductive behaviors) on three mental disorders, including bipolar disorder, major depressive disorder and schizophrenia. A series of filtering steps were taken to select eligible genetic instruments robustly associated with each of the traits. Inverse variance weighted was used for primary analysis, with alternative MR methods including MR-Egger, weighted median, and weighted mode estimate. Complementary methods were further used to detect pleiotropic bias. RESULTS: After Bonferroni correction and rigorous quality control, we identified that SES (educational attainment), smoking behaviors (smoking initiation, number of cigarettes per day), risky behaviors (adventurousness, number of sexual partners, automobile speeding propensity) and reproductive behavior (age at first birth) were causally associated with at least one of the mental disorders. CONCLUSIONS: MR study provides robust evidence that SES/IB play broad impacts on mental disorders.

Radiotherapy-Related Neurologic Complications in Patients with Nasopharyngeal Carcinoma: A Multicenter Epidemiologic Study in Southern China.

BACKGROUND: We aim at describing the incidence, potential predisposing factors, and progression of major radiotherapy-related neurologic complications (RRNC) in nasopharyngeal carcinoma (NPC)-endemic regions, especially southern China. METHODS: We performed a multicenter longitudinal retrospective study with clinical follow-ups in 22,302 patients with post-radiotherapy NPC between January 2003 and June 2017 covering three major residential areas. Epidemiology, potential predisposing/protective factors, clinicopathologic progression, and survival conditions of each RRNC were separately recorded and analyzed on the basis of their related clinical, radiologic, and laboratory parameters. RESULTS: 949 new cases of RRNCs occurred among the 22,302 patients with post-radiotherapy NPC during 101,714 person years' follow-up, which is equal to an incidence density rate of 9.3 new cases per 1000 person year. Radiation-induced cranial nerve palsy showed the highest incidence (2.68%, 597/22,302) with the earliest onset (median latency, 4.45 years) as well. Patients benefited from intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in both overall survival (median survival 13.2 years for IMRT vs. 8.3 years for CRT) and RRNC-free survival (except for epilepsy and cranial nerve palsy). Causes of death varied substantially between patients with or without RRNCs. CONCLUSIONS: Our study indicates a non-negligible incidence of RRNC spectrum in southern China in the past ten years. IMRT is one of the most significant protectors against development and progression of RRNCs. IMPACT: Our findings support the hypothesis that patients with NPC with preexisting predispositions would receive long-term benefits from IMRT and other dose-related modulations (like hyperfractionation and dose conformation).

Decreased RNA m6A methylation enhances the process of the epithelial mesenchymal transition and vasculogenic mimicry in glioblastoma.

RNA N6-methyladenosine (m6A) modification is gradually thought to be an active participant in the considerable biological processes of glioblastoma (GB), providing us with a novel insight for exploring this disease. However, the role of RNA m6A modification during the epithelial mesenchymal transition (EMT) or vasculogenic mimicry (VM) progression has not been investigated in GB. Here we performed a research to validate the impact exerted by AlkB homolog 5 (ALKBH5), one of "erasers" for RNA m6A and methyltransferase-like 3 (METTL3) which adds m6A modification to the RNAs on the progression of EMT and VM in GB. In this study, we demonstrate that the m6A levels of RNAs were reduced in GB cells and glioma tissues. Patients with high mRNA expression of ALKBH5 acquired relatively shorter median overall survival (OS) time, while patients with relatively high expression of MEETL3 prolonged their disease free survival. ALKBH5 enhanced GB cell proliferation and influenced cell cycle in vitro. Decreased RNA m6A methylation enhanced the progression of the EMT and VM in glioblastoma cells. ALKBH5 strengthened glioblastoma growth and enhanced the EMT and VM process of glioblastoma in vivo. Our study uncovers that RNA m6A methylation suppresses the process of EMT and VM in glioblastoma, providing a new perspective to seek for a potential therapeutic target for GB.

Exploring stroke risk and prevention in China: insights from an outlier.

In contrast to the declining trend in most regions worldwide, the incidence of stroke is increasing in China and is leading to an alarming burden for the national healthcare system. In this review, we have generated new insights from this outlier, and we aim to provide new information that will help decrease the global stroke burden, especially in China and other regions sharing similar problems with China. First of all, several unsolved aspects fundamentally accounting for this discrepancy were promising, including the serious situation of hypertension management, underdiagnosis of atrial fibrillation and underuse of anticoagulants, and unhealthy lifestyles (e.g., heavy smoking). In addition, efforts for further alleviating the incidence of stroke were recommended in certain fields, including targeted antiplatelet regimes and protections from cold wave-related stroke. Furthermore, advanced knowledge about cancer-related strokes, recurrent strokes and the status preceding stroke onset that we called stroke-prone status herein, is required to properly mitigate patient stroke risk, and to provide improved outcomes for patients after a stroke has occurred.

Iron Status May Not Affect Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

BACKGROUND: Observational studies have shown an association of increased iron status with a higher risk of amyotrophic lateral sclerosis (ALS). Iron status might be a novel target for ALS prevention if a causal relationship exists. We aimed to reveal the causality between iron status and ALS incidence using a large two-sample Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms (SNPs) for iron status were identified from a genome-wide association study (GWAS) on 48,972 individuals. The outcome data came from the largest ALS GWAS to date (20,806 cases; 59,804 controls). We conducted conservative analyses (using SNPs with concordant change of biomarkers of iron status) and liberal analyses (using SNPs associated with at least one of the biomarkers of iron status), with inverse variance weighted (IVW) method as the main analysis. We then performed sensitivity analyses including weighted median, MR-Egger and MR-pleiotropy residual sum and outlier, as well as leave-one-out analysis to detect pleiotropy. RESULTS: In the conservative analyses, we found no evidence of association between four biomarkers of iron status and ALS using IVW method with odds ratio (OR) 1.00 [95% confidence interval (CI): 0.90-1.11] per standard deviation (SD) increase in iron, 0.96 (95% CI: 0.77-1.21) in ferritin, 0.99 (95% CI: 0.92-1.07) in transferrin saturation, and 1.04 (95% CI: 0.93-1.16) in transferrin. Findings from liberal analyses were similar, and sensitivity analyses suggested no pleiotropy detected (all p > 0.05). CONCLUSION: Our findings suggest no causal effect between iron status and risk of ALS. Efforts to change the iron status to decrease ALS incidence might be impractical.

Idebenone attenuates cerebral inflammatory injury in ischemia and reperfusion via dampening NLRP3 inflammasome activity.

BACKGROUND: Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R. METHODS: I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed. RESULTS: We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume. INTERPRETATION: Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke.

An miR-340-5p-macrophage feedback loop modulates the progression and tumor microenvironment of glioblastoma multiforme.

MicroRNAs (miRNAs) have been shown to be involved in the progression and tumor microenvironment of glioblastoma multiforme (GBM). Our previous research has indicated that miR-340-5p has an antitumor effect in vitro. However, the role of miR-340-5p in GBM has not been fully elucidated. Here, we show that downregulation of miR-340-5p in GBM is correlated with tumor size, recurrence, and poor survival. Moreover, we found that miR-340-5p levels are correlated with the density of tumor-associated macrophages (TAMs) and M2-polarized TAMs in GBM. Biofunctional investigations revealed that downregulation of miR-340-5p promoted TAM recruitment and M2-TAMs polarization in vitro and in vivo. In addition, we found that upregulation of miR-340-5p inhibited tumor growth and was associated with good prognosis in vivo. Through gene expression profiles and bioinformatics analysis, we showed that miR-340-5p directly targets POSTN, which recruited TAMs through integrin αvß3. Downregulation of miR-340-5p in GBM did not induce the differentiation of TAMs into polarized M2 cells but was able to promote the M2 polarization of TAMs through directly targeting LTBP-1. Furthermore, we found that M2-TAMs promoted tumorigenesis and were associated with a poor prognosis in vivo. In an in vitro study, we demonstrated that M2-TAMs inhibited miR-340-5p expression in GBM cells by upregulation of TGFß-1, which increased HMGA-2 expression in GBM. A ChIP assay confirmed that HMGA-2 transcriptionally suppressed miR-340-5p expression. Patients with low-miR-340-5p expression, high CD163, high POSTN, high LIBP1 levels, and high HMGA-2 had a poor prognosis with shorter overall survival, confirming data from the TCGA database. These findings suggest that an miR-340-5p-macrophage feedback loop modulates the progression and tumor microenvironment of GBM and may represent a prognostic biomarker and therapeutic strategy for GBM.

Cognitive Performance Concomitant With Vision Acuity Predicts 13-Year Risk for Mortality.

Objective: To assess the joint impact of cognitive performance and visual acuity on mortality over 13-year follow-up in a representative US sample. Methods: Data from National Health and Nutrition Examination Survey (NHANES) participants (≥18 years old) were linked with the death record data of the National Death Index (NDI) with mortality follow-up through December 31, 2011. Cognitive performance was evaluated by the Digit Symbol Substitution Test (DSST) and cognitive performance impairment was defined as the DSST score equal to or less than the median value in the study population. Visual impairment (VI) was defined as presenting visual acuity worse than 20/40 in the better-seeing eye. Risks of all-cause and specific-cause mortality were estimated with Cox proportional hazards models after adjusting for confounders. Results: A total of 2,550 participants 60 years and older from two waves of (NHANES, 1999-2000, 2001-2002) were included in the current analysis. Over a median follow-up period of 9.92 years, 952 (35.2%) died of all causes, of whom 239 (23.1%), 224 (24.0%), and 489 (52.9%) died from cardiovascular disease (CVD), cancer, and non-CVD/non-cancer mortality, respectively. Cognitive performance impairment and VI increased the odds for mortality. Co-presence of VI among cognitive impaired elderly persons predicted nearly a threefold increased risk of all-cause mortality [hazard ratios (HRs), 2.74; 95% confidence interval (CI), 2.02-3.70; P < 0.001) and almost a fourfold higher risk of non-CVD/non-cancer mortality (HR, 3.72; 95% CI, 2.30-6.00; P < 0.001) compared to having neither impairment. Conclusion: People aged 60 years and over with poorer cognitive performance were at higher risk of long-term mortality, and were especially vulnerable to further mortality when concomitant with VI. It is informative for clinical implication in terms of early preventive interventions.

Intrathecal Injection of Allogenic Bone Marrow-Derived Mesenchymal Stromal Cells in Treatment of Patients with Severe Ischemic Stroke: Study Protocol for a Randomized Controlled Observer-Blinded Trial.

Mesenchymal stromal cells (MSCs) can differentiate into multiple tissues. Preclinical studies have shown that MSC-based therapy is a potential new treatment approach for ischemic stroke. These results support the urgent need for further studies of MSC transplantation in the treatment of ischemic stroke in humans. Here, we develop a prospective, randomized, controlled, observer-blinded phase II trial to assess the clinical safety, feasibility, and therapeutic mechanisms of allogenic bone marrow-derived MSCs (BM-MSCs) by intrathecal infusion in the treatment of patients with cerebral infarction within the middle cerebral artery and with a National Institutes of Health Stroke Scale (NIHSS) score from 15 to 25. Sample size calculation has determined that a patient population of 118, with ischemic stroke between 30 and 90 days following onset, will be randomly divided into experimental (n = 59) and control (n = 59) groups. Then eligible patients will receive four intrathecal infusions of allogenic BM-MSCs (1 × 106 cells/kg body weight) once a week. All patients have detailed functional assessments and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. The primary outcome is the score on the modified Rankin Scale at 90 days after treatment, and the second outcomes include multiple indicators of safety and feasibility. And this trial has been registered as ChiCTR-INR-16008908 (25 July 2016).

[Thoracoscopic repair of congenital diaphragmatic hernia in neonates: a report of 47 cases].

OBJECTIVE: To review the application of thoracoscopic repair for treatment of congenital diaphragmatic hernia in neonates, so as to improve the cure rate. METHODS: Clinical data of 47 neonates with congenital diaphragmatic hernia receiving thoracoscopic repair from June 2012 to June 2017 were reviewed. The admission age, gestational age, birth weight, timing of diagnosis, hernia location, clinical manifestation, surgical timing, surgical method, operation time, postoperative mechanical ventilation time of patients were analyzed. RESULTS: There were 42 cases of left diaphragmatic hernia and 5 cases of right diaphragmatic hernia. Thirteen cases were diagnosed prenatally. Primary diaphragmatic repair was successfully accomplished under thoracoscope in 45 neonates without perioperative complications, while 2 patients were converted to open surgery. The average operation time was (63±13) min (42-150 min), the average blood loss was (3.0±1.7) mL (1.0-9.0 mL), and the average postoperative mechanical ventilation time was (3.9±1.4) d (2.0-11.0 d). Two patients died and the treatment was withdrawn in 3 patients with an overall cure rate of 89.4% (42/47). CONCLUSIONS: Thoracoscopic repair is effective and can be used as first-choice treatment of diaphragmatic hernia in neonates.

Corrigendum to "Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis".

[This corrects the article DOI: 10.1155/2017/1948985.].

Hyponatremia is a potential predictor of progression in radiation-induced brain necrosis: a retrospective study.

BACKGROUND: To investigate the prognostic value of hyponatremia, defined as serum sodium level < 135 mEq/L, in radiation-induced brain necrosis (RN) patients. METHODS: We performed a retrospective analysis of the RN patients (The patients included in our study had a history of primary cancers including nasopharyngeal carcinoma/glioma/oral cancer and received radiotherapy previously and then were diagnosed with RN) treated in Sun yat-sen Memorial Hospital from January 2013 to August 2015. Patients without cranial magnetic resonance imaging (MRI) scan and serum sodium data were excluded. Progression was identified when the increase of edema area ≥ 25% on the MRI taken in six months comparing with those taken at the baseline. Factors that might associate with prognosis of RN were collected. Multivariable logistic regression analyses were used to identify potential predictors. RESULTS: We total included 135 patients, 32 (23.7%) of them with hyponatremia and 36 (26.7%) with RN progression. Percentage of progression was roughly three fold in hyponatremia patients compared with nonhyponatremia patients (53.1% versus 18.4%), translating into a 5-fold increased odds ratio (P <  0.001). Multivariable analyses identified hyponatremia as a potential predictor of progression (OR, 4.82; 95% CI [1.94-11.94]; P = 0.001). CONCLUSIONS: Hyponatremia was identified as a potential predictor for the progression of patients with RN. Hyponatremia management in patients with RN should be paid much more concern in clinical practice.

Statin treatment may lower the risk of postradiation epilepsy in patients with nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to clarify the effect of statins on preventing the risk of postradiation epilepsy. METHODS: We performed a retrospective analysis of neurological nasopharyngeal carcinoma patients with a history of radiotherapy. Patients with a history of epilepsy before radiation and those who received prophylactically antiepileptic treatment were excluded. The demographic and clinical data of these patients were collected through chart review. We used Kaplan-Meier analysis (log-rank test) to examine the effect of statins on epilepsy-free survival. Cox regression analysis was utilized to identify independent predictive variables. RESULTS: Our study included 532 patients (405 males and 127 females) with a mean follow-up of 28.1 months. During follow-up, 471 (88.5%) patients developed radiation-induced brain necrosis (RN). Within a mean latency of 24.1 months, 88 (16.5%) patients experienced epilepsy, of whom 27 (27 of 88, 30.7%) patients suffered from epilepsy before the diagnosis of RN. Thirty-six (36 of 88, 40.9%) cases of epilepsy occurred after RN onset, and in 22 cases (22 of 88, 25.0%) epilepsy was the first presentation of RN. Three patients suffered from epilepsy but did not have RN. Eighty-eight patients in our cohort were treated with statins because of hyperlipidemia or prevention of cardiocerebrovascular diseases, of whom six (6.8%) developed epilepsy, whereas in those without statin, the epileptic rate was 18.5%. Log-rank test found that there was a significant difference in epilepsy-free survival between patients who used statins and those who did not (p = 0.016). After adjusting for confounding variables, multivariate Cox regression analysis revealed that statin use could still significantly reduce the risk of epilepsy after radiation (hazard ratio = 0.36, 95% confidence interval = 0.15-0.82, p = 0.015). However, for the patients who already suffered from RN, statin treatment did not lower the risk of post-RN epilepsy. SIGNIFICANCE: Early statin use may reduce the risk of postradiotherapy epilepsy in patients with nasopharyngeal carcinoma.

Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis.

Radiation-induced brain injury (RI) commonly occurs in patients who received head and neck radiotherapy. However, the mechanism of RI remains unclear. We aimed to evaluate whether pyroptosis was involved in RI and the impact of mesenchymal stem cells (MSCs) on it. BALB/c male mice (6-8 weeks) were cranially irradiated (15 Gy), and MSCs were transplanted into the bilateral cortex 2 days later; then mice were sacrificed 1 month later. Meanwhile, irradiated BV-2 microglia cells (10 Gy) were cocultured with MSCs for 24 hours. We observed that irradiated mice brains presented NLRP3 and caspase-1 activation. RT-PCR then indicated that it mainly occurred in microglia cells but not in neurons. Further, irradiated BV-2 cells showed pyroptosis and increased production of IL-18 and IL-1ß. RT-PCR also demonstrated an increased expression of several inflammasome genes in irradiated BV-2 cells, including NLRP3 and AIM2. Particularly, NLRP3 was activated. Knockdown of NLRP3 resulted in decreased LDH release. Noteworthily, in vivo, MSCs transplantation alleviated radiation-induced NLRP3 and caspase-1 activation. Moreover, in vitro, MSCs could decrease caspase-1 dependent pyroptosis, NLRP3 inflammasome activation, and ROS production induced by radiation. Thus, our findings proved that microglia pyroptosis occurred in RI. MSCs may act as a potent therapeutic tool in attenuating pyroptosis.

VEGF induces angiogenesis in a zebrafish embryo glioma model established by transplantation of human glioma cells.

Zebrafish (Danio rerio) is becoming an increasingly popular vertebrate cancer model. In this study, we established a xenotransplanted zebrafish embryo glioma model to further investigate the molecular mechanisms of tumor angiogenesis. We find that the glioma cell line U87 can survive, proliferate and induce additional SIV branches in zebrafish embryos. In addition, by the means of in situ hybridization and quantitive RT-PCR analyses we find that the transplanted U87 cells can induce the ectopic zebrafish vascular endothelial growth factor A (VEGF A) and its receptor VEGFR2/KDR mRNA expression and increase their expression levels, resulting in additional SIV branches.