Integrated network pharmacology and experimental verification to reveal the role of Shezhi Huangling Decoction against glioma by inactivating PI3K/Akt-HIF1A axis.

Shezhi Huangling Decoction (SHD) has been proven clinically effective in regulating metabolic and immune homeostasis in the treatment of glioma. The investigation aimed to deconstruct the active constituents and mechanisms of SHD. Effects of SHD on malignant characteristics of HS683 and KNS89 cells have been investigated by CCK-8, clone formation, flow cytometry, and Transwell assays. A mouse xenograft model was established to assess the effect of SHD or SHD + temozolomide (TMZ) in vivo. A total of 461 constituents were found from SHD in UPLC/Q-TOF-MS/MS analysis. Functional enrichment analysis showed that pathway in cancer, proteoglycans in cancer, regulation of epithelial cell proliferation, inflammation/immune, gliogenesis, brain development, cell adhesion, and autophagy could participate in the treatment of SHD. Additionally, 9 hub genes (AKT1, TP53, CTNNB1, STAT3, EGFR, VEGFA, PIK3CA, ERBB2, and HIF1A) were identified as hub genes. Moreover, we found that SHD may greatly reduce the migration and accelerate apoptosis of HS683 and KNS89 cells. Additionally, SHD coordinates TMZ to restrict tumor growth were found in the mice. Our results suggest that the malignant behaviors of glioma cells are suppressed by SHD and the mechanism may be closing on the inhibition of the PI3K/Akt-HIF1A axis. SHD may serve as a synergistic therapeutic choice for TMZ to suppress glioblastoma growth.

Regulation mechanism of endoplasmic reticulum stress on metabolic enzymes in liver diseases.

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca2+ storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive. When ER stress is severe and sustained, it typically provokes cell death through multiple approaches. It is well documented that ER stress and metabolic deregulation are functionally intertwined, both are considered contributing factors to the pathogenesis of liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), ischemia/reperfusion (I/R) injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatocytes are rich in smooth and rough ER, which harbor metabolic enzymes that are capable of sensing alterations in various nutritional status and external stimuli. Extensive research has focused on the molecular mechanism linking ER stress with metabolic enzymes. The purpose of this review is to summarize the current knowledge regarding the effects of ER stress on metabolic enzymes in various liver diseases and to provide potential therapeutic strategies for chronic liver diseases via targeting UPR.

A Clinical-Radiomics Nomogram for Predicting Early Ischemic Stroke Risk in Patients with Transient Ischemic Attack.

OBJECTIVE: To develop and validate a clinical-radiomics nomogram for predicting early ischemic stroke risk in patients who sustain a transient ischemic attack (TIA). METHODS: A retrospective training dataset (n = 76) and a prospective validation dataset (n = 34) of patients with TIA were studied. Image processing was performed using ITK-snap and Artificial Intelligent Kit. Radiomics features were selected in R. A nomogram predicting recurrent TIA/stroke in 90 days as a recurrent ischemic event was established. Model performance was assessed by computing the receiver operating characteristic curve and decision curve analysis (DCA). RESULTS: We found a higher proportion of diabetes and hypertension in the patients with recurrent TIA compared with the stable patients in both the training and validation datasets (P < 0.05). Recurrent patients had significantly higher ABCD2 scores and plaque scores compared to stable patients. ABCD2 score and necrotic/lipid core area were independent risk factors for recurrent ischemic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.47-6.40; and OR, 1.20; 95% CI, 1.07-1.41, respectively). The radiomics model had area under the curve values of 0.737 (95% CI, 0.715-0.878) in the training dataset and 0.899 (95% CI, 0.706-0.936) in the validation dataset, which was superior to the ABCD2 score and plaque model for predicting stroke recurrence (P < 0.05). The nomogram predicting recurrent ischemic events was 0.923 (95% CI, 0.895-0.978) in the training dataset and 0.935 (95% CI, 0.830-0.959) in the validation dataset. DCA confirmed the clinical value of this nomogram. CONCLUSIONS: The nomogram, based on clinical ABCD2 score, carotid plaque components and radiomics score, shows good performance in predicting the risk of recurrent ischemic events in patients with TIA.

Xiaoke Bitong capsule alleviates inflammatory impairment via inhibition of the TNF signaling pathway to against diabetic peripheral neuropathy.

BACKGROUND: Xiaoke Bitong capsule (XBC) is a crude herbal compound believed to tonify qi, improve blood circulation, and alleviate blood stasis. It has been used as an herbal formula for the prevention and treatment of diabetic peripheral neuropathy (DPN) under the guidance of traditional Chinese medicine (TCM). However, the pharmacological mechanisms by which XBC ameliorates DPN remain poorly understood. The interaction between pro-inflammatory factors and the activation of tumor necrosis factor (TNF) plays a critical role in the underlying mechanisms of DPN. XBC may protect against DPN through the regulation of the TNF pathway. PURPOSE: Many studies show the association between DPN and nerve dysfunction, however, treatment options are limited. To identify specific therapeutic targets and active components of XBC that contribute to its anti-DPN effects, our study aimed to investigate the potential mechanism of action of XBC during the progression of DPN using a system pharmacology approach. METHODS: An approach involving UPLC-Q-TOF/MS and network pharmacology was used to analyze the compositions, potential targets, and active pathways of XBC. Further, models of streptozocin (STZ) induced mouse and glucose induced RSC96 cells were established to explore the therapeutic effects of XBC. High glucose induced RSC96 cells were pretreated with small interfering RNA (siRNA) to identify potential therapeutic targets of DPN. RESULTS: Seventy-one active compositions of XBC and five potential targets, including mitogen-activated protein kinase 8 (MAPK), interleukin-6 (IL-6), poly-ADP-ribose polymerase-1 (PARP1), vascular endothelial growth factor A (VEGFA), and transcription factor p65 (NF-κB), were considered as the potential regulators of DPN. In addition, the results revealed that the TNF signaling pathway was closely related to DPN. Moreover, DPN contributed to the decreased expressions of PI3K and AKT, increased TNF-α and IL-1ß in RSC96 cells, which were both reversed by XBC or TNF-α siRNA. CONCLUSION: XBC could protect against DPN by inhibiting the release of pro-inflammatory cytokines and regulating the activation of the TNF signaling pathway, further accelerating neurogenesis, and alleviating peripheral nerve lesions. Therefore, this study highlights the therapeutic value of XBC for DPN.

Pan-cancer analysis identifies olfactory receptor family 7 subfamily A member 5 as a potential biomarker for glioma.

Background: Human olfactory receptors (ORs) account for approximately 60% of all human G protein-coupled receptors. The functions of ORs extend beyond olfactory perception and have garnered significant attention in tumor biology. However, a comprehensive pan-cancer analysis of ORs in human cancers is lacking. Methods: Using data from public databases, such as HPA, TCGA, GEO, GTEx, TIMER2, TISDB, UALCAN, GEPIA2, and GSCA, this study investigated the role of olfactory receptor family 7 subfamily A member 5 (OR7A5) in various cancers. Functional analysis of OR7A5 in LGG and GBM was performed using the CGGA database. Molecular and cellular experiments were performed to validate the expression and biological function of OR7A5 in gliomas. Results: The results revealed heightened OR7A5 expression in certain tumors, correlating with the expression levels of immune checkpoints and immune infiltration. In patients with gliomas, the expression levels of OR7A5 were closely associated with adverse prognosis, 1p/19p co-deletion status, and wild-type IDH status. Finally, in vitro experiments confirmed the inhibitory effect of OR7A5 knockdown on the proliferative capacity of glioma cells and on the expression levels of proteins related to lipid metabolism. Conclusion: This study establishes OR7A5 as a novel biomarker, potentially offering a novel therapeutic target for gliomas.

An inverse association of dietary choline with atherosclerotic cardiovascular disease among US adults: a cross-sectional NHANES analysis.

BACKGROUND: The role of diet choline in atherosclerotic cardiovascular disease (ASCVD) is uncertain. Findings from animal experiments are contradictory while there is a lack of clinical investigations. This study aimed to investigate the association between choline intake and ASCVD based on individuals from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study was conducted in 5525 individuals from the NHANES between 2011 and 2018. Participants were categorized into the ASCVD (n = 5015) and non-ASCVD (n = 510) groups. Univariable and multivariable-adjusted regression analyses were employed to investigate the relationship between diet choline and pertinent covariates. Logistic regression analysis and restricted cubic spline analysis were used to evaluate the association between choline intake and ASCVD. RESULTS: ASCVD participants had higher choline intake compared to those without ASCVD. In the higher tertiles of choline intake, there was a greater proportion of males, married individuals, highly educated individuals, and those with increased physical activity, but a lower proportion of smokers and drinkers. In the higher tertiles of choline intake, a lower proportion of individuals had a history of congestive heart failure and stroke. After adjusting for age, gender, race, ethnicity, and physical activity, an inverse association between choline intake and heart disease, stroke, and ASCVD was found. A restricted cubic spline analysis showed a mirrored J-shaped relationship between choline and ASCVD, stroke and congestive heart failure in males. There was no association between dietary choline and metabolic syndrome. CONCLUSION: An inverse association was observed between choline intake and ASVCD among U.S. adults. Further large longitudinal studies are needed to test the causal relationship of choline and ASVCD.

Integrated analysis of single-cell sequencing and weighted co-expression network identifies a novel signature based on cellular senescence-related genes to predict prognosis in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a highly aggressive cancer with heavy mortality rates and poor prognosis. Cellular senescence exerts a pivotal influence on the development and progression of various cancers. However, the underlying effect of cellular senescence on the outcomes of patients with GBM remains to be elucidated. METHODS: Transcriptome RNA sequencing data with clinical information and single-cell sequencing data of GBM cases were obtained from CGGA, TCGA, and GEO (GSE84465) databases respectively. Single-sample gene set enrichment analysis (ssGSEA) analysis was utilized to calculate the cellular senescence score. WGCNA analysis was employed to ascertain the key gene modules and identify differentially expressed genes (DEGs) associated with the cellular senescence score in GBM. The prognostic senescence-related risk model was developed by least absolute shrinkage and selection operator (LASSO) regression analyses. The immune infiltration level was calculated by microenvironment cell populations counter (MCPcounter), ssGSEA, and xCell algorithms. Potential anti-cancer small molecular compounds of GBM were estimated by "oncoPredict" R package. RESULTS: A total of 150 DEGs were selected from the pink module through WGCNA analysis. The risk-scoring model was constructed based on 5 cell senescence-associated genes (CCDC151, DRC1, C2orf73, CCDC13, and WDR63). Patients in low-risk group had a better prognostic value compared to those in high-risk group. The nomogram exhibited excellent predictive performance in assessing the survival outcomes of patients with GBM. Top 30 potential anti-cancer small molecular compounds with higher drug sensitivity scores were predicted. CONCLUSION: Cellular senescence-related genes and clusters in GBM have the potential to provide valuable insights in prognosis and guide clinical decisions.

TREM1 as a novel prognostic biomarker and tumor immune microenvironment evaluator in glioma.

Glioma is the most malignant tumor in the central nervous system with a poor prognosis. The tumor immune microenvironment plays a crucial role in glioma formation and progress. TREM1, as a vital immune regulator, has not been investigated in glioma. This study aims to explore the role of TREM1 in prognosis and tumor immune microenvironment of glioma. The mRNA expression level of TREM1 was collected from TCGA and GEO databases. The correlations between the clinic-pathological features and TREM1 expression were analyzed using Cox regression analysis. Kaplan-Meier was used to evaluate the effect of TREM1 on OS. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes were performed to analyze the functional annotations and signaling pathways of the TREM1 coexpression genes. ESTIMATE and TIMER explored the correlations between TREM1 and immune cell infiltration. Spearman correlation analysis was conducted to examine the association between the TREM1 and immune checkpoint expression. The expression level of TREM1 was significantly increased in glioma. TREM1 overexpression was positively related to poor prognosis, higher World Health Organization grade, isocitrate dehydrogenase wildtype, and 1p/19q non-codeletion. TREM1 coexpression genes were mainly related to immunoregulation and inflammatory response. TREM1 participated in the initiation and progression of glioma by regulating immune cell infiltration and expression of immune checkpoints. TREM1 is an effective prognostic and diagnostic biomarker in glioma. It can be adopted as a novel predictor for clinical prognosis, pathological characteristics, and immune microenvironment in glioma patients.

Efficacy of a novel glioma therapy based on ferroptosis induced by layered double hydroxide loaded with simvastatin.

Glioma is the most common primary malignant tumor of the nervous system that starts in the glial cells. Its high invasiveness and recurrence pose major challenges to its effective treatment. Ferroptosis is a new type of programmed cell death characterized by intracellular iron overload and accumulation of lipid peroxides. Existing studies have demonstrated the efficacy of targeted ferroptosis therapy in the treatment of glioma. In this study, folic acid (FA)-modified layered double hydroxide loaded with simvastatin (SIM), a ferroptosis drug, was used to prepare a novel ferroptosis nanodrug (FA-LDH@SIM). The prepared nanodrug improved the therapeutic effect of SIM on glioma. Compared with free SIM, FA-LDH@SIM showed greater cytotoxicity, significantly inhibited glioma cell proliferation, and significantly inhibited glioma invasion and migration ability. Furthermore, SIM could induce changes in certain ferroptosis indicators, including increased intracellular LPO, ROS and MDA level, decreased GSH production, increased divalent iron level, and changes in mitochondrial morphology. Further experiments revealed that SIM induced ferroptosis in tumor cells by down-regulating HMGCR expression and inhibiting the mevalonate pathway to down-regulate GPX4 expression. In addition, the FA-LDH@SIM group significantly inhibited tumor growth after treatment in the animal glioma model. These results indicate that the FA-LDH@SIM nanodrug delivery system exhibits excellent anti-tumor effects both in vitro and in vivo, and is an effective method for the treatment of glioma.

Neuroimaging Study of Brain Functional Differences in Generalized Anxiety Disorder and Depressive Disorder.

Generalized anxiety disorder (GAD) and depressive disorder (DD) are distinct mental disorders, which are characterized by complex and unique neuroelectrophysiological mechanisms in psychiatric neurosciences. The understanding of the brain functional differences between GAD and DD is crucial for the accurate diagnosis and clinical efficacy evaluation. The aim of this study was to reveal the differences in functional brain imaging between GAD and DD based on multidimensional electroencephalogram (EEG) characteristics. To this end, 10 min resting-state EEG signals were recorded from 38 GAD and 34 DD individuals. Multidimensional EEG features were subsequently extracted, which include power spectrum density (PSD), fuzzy entropy (FE), and phase lag index (PLI). Then, a direct statistical analysis (i.e., ANOVA) and three ensemble learning models (i.e., Random Forest (RF), Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost)) were used on these EEG features for the differential recognitions. Our results showed that DD has significantly higher PSD values in the alpha1 and beta band, and a higher FE in the beta band, in comparison with GAD, along with the aberrant functional connections in all four bands between GAD and DD. Moreover, machine learning analysis further revealed that the distinct features predominantly occurred in the beta band and functional connections. Here, we show that DD has higher power and more complex brain activity patterns in the beta band and reorganized brain functional network structures in all bands compared to GAD. In sum, these findings move towards the practical identification of brain functional differences between GAD and DD.

Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.

The tumor microenvironment (TME) is a crucial driving factor for tumor progression and it can hinder the body's immune response by altering the metabolic activity of immune cells. Both tumor and immune cells maintain their proliferative characteristics and physiological functions through transporter-mediated regulation of nutrient acquisition and metabolite efflux. Transporters also play an important role in modulating immune responses in the TME. In this review, we outline the metabolic characteristics of the TME and systematically elaborate on the effects of abundant metabolites on immune cell function and transporter expression. We also discuss the mechanism of tumor immune escape due to transporter dysfunction. Finally, we introduce some transporter-targeted antitumor therapeutic strategies, with the aim of providing new insights into the development of antitumor drugs and rational drug usage for clinical cancer therapy.

Functionalized nanoparticles crossing the brain-blood barrier to target glioma cells.

Glioma is the most common tumor of the central nervous system (CNS), with a 5-year survival rate of <35%. Drug therapy, such as chemotherapeutic and immunotherapeutic agents, remains one of the main treatment modalities for glioma, including temozolomide, doxorubicin, bortezomib, cabazitaxel, dihydroartemisinin, immune checkpoint inhibitors, as well as other approaches such as siRNA, ferroptosis induction, etc. However, the filter function of the blood-brain barrier (BBB) reduces the amount of drugs needed to effectively target CNS tumors, making it one of the main reasons for poor drug efficacies in glioma. Thus, finding a suitable drug delivery platform that can cross the BBB, increase drug aggregation and retainment in tumoral areas and avoid accumulation in non-targeted areas remains an unsolved challenge in glioma drug therapy. An ideal drug delivery system for glioma therapy should have the following features: (1) prolonged drug life in circulation and effective penetration through the BBB; (2) adequate accumulation within the tumor (3) controlled-drug release modulation; (4) good clearance from the body without significant toxicity and immunogenicity, etc. In this regard, due to their unique structural features, nanocarriers can effectively span the BBB and target glioma cells through surface functionalization, providing a new and effective strategy for drug delivery. In this article, we discuss the characteristics and pathways of different nanocarriers for crossing the BBB and targeting glioma by listing different materials for drug delivery platforms, including lipid materials, polymers, nanocrystals, inorganic nanomaterials, etc.

The evaluation of six genes combined value in glioma diagnosis and prognosis.

PURPOSE: Glioma is the most common and fatal type of brain tumour. Owing to its aggressiveness and lethality, early diagnosis and prediction of patient survival are very important. This study aimed to identify key genes and biomarkers for glioma that can guide clinicians in making rapid diagnosis and prognostication. METHODS: Data mining of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Repository of Molecular Brain Neoplasia Data, and Genotype-Tissue Expression Project brain expression data revealed significantly differentially expressed genes (DEGs), and the risk scores of individual patients were calculated. WGCNA was utilized to screen for genes most related to clinical diagnosis. Prognostic genes associated with glioma were selected via combining the LASSO regression with univariate and multivariate Cox regression and protein-protein interaction network analyses. Then, a nomogram was constructed. And CGGA dataset was utilized to validated. The protein expression levels of the signature were detected using the human protein atlas. Drug response prediction was carried out using the package "pRRophetic". RESULTS: A six-gene signature (KLF6, CHI3L1, SERPINE1, ANGPT2, TGFBR1, and PTX3) was identified and used to stratify patients into low- and high-risk groups. Survival, ROC curve, and Cox analyses clarified that the six hub genes were a favourable independent prognostic factor for patients with glioma. A nomogram was set up by integrating clinical parameters with risk signatures, showing high precision for predicting 2-, 3-, 4-, 5-years survival. In addition, the expression of most genes was consistent with protein expression. Furthermore, the sensitivity to the top ten drugs in the GDSC database of the high-risk group was significantly higher than the low-risk group. CONCLUSION: Based on genetic profiles and clinicopathological features, including age, grade, isocitrate dehydrogenase mutation status, we constructed a comprehensive prognostic model for patients with glioma. These signatures can be regarded as biomarkers to predict the prognosis of gliomas, possibly providing more therapeutic strategies for future clinical research.

Brain network analysis reveals convergent and divergent aberrations between mild stroke patients with cortical and subcortical infarcts during cognitive task performing.

Although consistent evidence has revealed that cognitive impairment is a common sequela in patients with mild stroke, few studies have focused on it, nor the impact of lesion location on cognitive function. Evidence on the neural mechanisms underlying the effects of mild stroke and lesion location on cognitive function is limited. This prompted us to conduct a comprehensive and quantitative study of functional brain network properties in mild stroke patients with different lesion locations. Specifically, an empirical approach was introduced in the present work to explore the impact of mild stroke-induced cognitive alterations on functional brain network reorganization during cognitive tasks (i.e., visual and auditory oddball). Electroencephalogram functional connectivity was estimated from three groups (i.e., 40 patients with cortical infarctions, 48 patients with subcortical infarctions, and 50 healthy controls). Using graph theoretical analysis, we quantitatively investigated the topological reorganization of functional brain networks at both global and nodal levels. Results showed that both patient groups had significantly worse behavioral performance on both tasks, with significantly longer reaction times and reduced response accuracy. Furthermore, decreased global and local efficiency were found in both patient groups, indicating a mild stroke-related disruption in information processing efficiency that is independent of lesion location. Regarding the nodal level, both divergent and convergent node strength distribution patterns were revealed between both patient groups, implying that mild stroke with different lesion locations would lead to complex regional alterations during visual and auditory information processing, while certain robust cognitive processes were independent of lesion location. These findings provide some of the first quantitative insights into the complex neural mechanisms of mild stroke-induced cognitive impairment and extend our understanding of underlying alterations in cognition-related brain networks induced by different lesion locations, which may help to promote post-stroke management and rehabilitation.

Ramelteon improves blood-brain barrier of focal cerebral ischemia rats to prevent post-stroke depression via upregulating occludin.

Post-stroke depression (PSD) negatively affects the prognosis of post-stroke animals. Ramelteon has neuroprotection for chronic ischemia animals, but the effect and the biological mechanism of it on PSD is still unclear. This study explored the effects of ramelteon with prophylactic administration on blood-brain barrier in rats with middle cerebral artery occlusion (MCAO) and the oxygen-glucose deprivation/reperfusion (OGD/R) bEnd.3 cells and found that ramelteon pretreatment improved the depressive-like behaviors and decreased infarct area in MCAO rats. Also, this study found ramelteon pretreatment improved viability and inhibited permeability in OGD/R cells. In addition, this study found that MCP-1, TNF-α, and IL-1 levels were raised in the MCAO rats and that occludin protein and mRNA levels were decreased in the MCAO and the OGD/R models, while the Egr-1 level was up-regulated. All of these were antagonized by ramelteon pretreatment. In addition, overexpression of Egr-1 could reverse the effect of 100 nM ramelteon pretreatment on FITC and occludin levels in OGD/R cells. In short, this study has demonstrated that the protective effect on PSD of ramelteon pretreatment on MCAO rats is related to the development of BBB permeability and that ramelteon regulates occludin to protect the BBB by inhibiting Egr-1.

Altered Functional Brain Network Structure between Patients with High and Low Generalized Anxiety Disorder.

To investigate the differences in functional brain network structures between patients with a high level of generalized anxiety disorder (HGAD) and those with a low level of generalized anxiety disorder (LGAD), a resting-state electroencephalogram (EEG) was recorded in 30 LGAD patients and 21 HGAD patients. Functional connectivity between all pairs of brain regions was determined by the Phase Lag Index (PLI) to construct a functional brain network. Then, the characteristic path length, clustering coefficient, and small world were calculated to estimate functional brain network structures. The results showed that the PLI values of HGAD were significantly increased in alpha2, and significantly decreased in the theta and alpha1 rhythms, and the small-world attributes for both HGAD patients and LGAD patients were less than one for all the rhythms. Moreover, the small-world values of HGAD were significantly lower than those of LGAD in the theta and alpha2 rhythms, which indicated that the brain functional network structure would deteriorate with the increase in generalized anxiety disorder (GAD) severity. Our findings may play a role in the development and understanding of LGAD and HGAD to determine whether interventions that target these brain changes may be effective in treating GAD.

Machine Learning Techniques Reveal Aberrated Multidimensional EEG Characteristics in Patients with Depression.

Depression has become one of the most common mental illnesses, causing serious physical and mental harm. However, there remain unclear and uniform physiological indicators to support the diagnosis of clinical depression. This study aimed to use machine learning techniques to investigate the abnormal multidimensional EEG features in patients with depression. Resting-state EEG signals were recorded from 41 patients with depression and 34 healthy controls. Multiple dimensional characteristics were extracted, including power spectral density (PSD), fuzzy entropy (FE), and phase lag index (PLI). These three different dimensional characteristics with statistical differences between two groups were ranked by three machine learning algorithms. Then, the ranked characteristics were placed into the classifiers according to the importance of features to obtain the optimal feature subset with the highest classification accuracy. The results showed that the optimal feature subset contained 86 features with the highest classification accuracy of 98.54% ± 0.21%. According to the statistics of the optimal feature subset, PLI had the largest number of features among the three categories, and the number of beta features was bigger than other rhythms. Moreover, compared to the healthy controls, the PLI values in the depression group increased in theta and beta rhythms, but decreased in alpha1 and alpha2 rhythms. The PSD of theta and beta rhythms were significantly greater in depression group than that in healthy controls, and the FE of beta rhythm showed the same trend. These findings indicate that the distribution of abnormal multidimensional features is potentially useful for the diagnosis of depression and understanding of neural mechanisms.

Comparison of clinical characteristics with spontaneous intracranial hypotension complicated with subdural hematoma between surgical treatment and non-surgical treatment.

OBJECTIVES: The aim of this current study was to analyze the possible surgical predictive factors about spontaneous intracranial hypotension (SIH) complicated with subdural hematoma (SDH). METHODS: 178 patients diagnosed with both SIH and SDH were retrospectively reviewed. All the participants were divided into as EBP group (BPG) and surgical treatment group (STG). The demographic, clinical manifestations, radiographic and treatment data of the two groups were collected and compared by the electrical medical history system. RESULTS: The male patients accounted for the majority in the STG (77.88 %), which was significantly larger than those in the BPG(p = 0.004). Patients who regularly smoked and drunk alcohol in the STG group were significantly greater than those in the BPG group (p(smoking)= 0.049, p(drinking)= 0.014). The headache occurring in the temporal position in the STG accounted for 44.44 % which was significantly greater than those in the BPG (25.17 %, p = 0.040). The durations days of symptoms were 54.85 ± 34.78 and 33.72 ± 34.97 in the STG and BPG respectively (p = 0.005). The midline shift degree in the STG was also significantly greater than that in the BPG (p = 0.001). The largest hematoma depth in the STG was significantly greater than that in the BPG (p = 0.000). The frequency of blood patch in the STG was significantly greater than that in the BPG(p = 0022). CONCLUSION: Male, unhealthy living habits, temporal headache, duration of headache, midline shift, hematoma depth and blood patch frequency were possible related factors with the poor outcome of blood patch and surgical treatment.

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progression by creating an energy crisis for preneoplastic cells, resulting in antiproliferative effects. These effects are referred to as chemopreventive effects mediated by an antioxidant mechanism. In addition, antioxidants minimize chemotherapy-induced nonspecific organ toxicity and prolong survival. Antioxidants also support the prooxidant chemistry that demonstrate chemotherapeutic potential, particularly at high or pharmacological doses and trigger OS by promoting free radical production, which is essential for activating cell death pathways. A growing body of evidence also revealed the roles of exogenous antioxidants as adjuvants and their ability to reverse chemoresistance. In this review, we explain the influences of different exogenous and endogenous antioxidants on brain cancers with reference to their chemopreventive and chemotherapeutic roles. The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. Finally, the review hypothesized that both pro- and antioxidant roles are involved in the anticancer mechanisms of the antioxidant molecules by killing neoplastic cells and inhibiting tumor recurrence followed by conventional cancer treatments. The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. Finally, we also mention the influencing factors that regulate the pharmacology of the exogenous antioxidants in brain cancer treatment. In conclusion, to achieve consistent clinical outcomes with antioxidant treatments in brain cancers, rigorous mechanistic studies are required with respect to the types, forms, and stages of brain tumors. The concomitant treatment regimens also need adequate consideration.

Bifidobacterium spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses.

Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis. The intestinal microbiome is increasingly appreciated to play a crucial role in modulation of AP disease outcome, but limited information is available about the identity and mechanism of action for specific commensal bacteria involved in AP-associated inflammation. Here we show that Bifidobacteria, particularly B. animalis, can protect against AP by regulating pancreatic and systemic inflammation in germ-free (GF) and oral antibiotic-treated (Abx) mouse models. Colonization by B. animalis and administration of its metabolite lactate protected Abx and GF mice from AP by reducing serum amylase concentration, ameliorating pancreatic lesions and improving survival rate after retrograde injection of sodium taurocholate. B. animalis relieved macrophage-associated local and systemic inflammation of AP in a TLR4/MyD88- and NLRP3/Caspase1-dependent manner through its metabolite lactate. Supporting our findings from the mouse study, clinical AP patients exhibited a decreased fecal abundance of Bifidobacteria that was inversely correlated with the severity of systemic inflammatory responses. These results may shed light on the heterogeneity of clinical outcomes and drive the development of more efficacious therapeutic interventions for AP, and potentially for other inflammatory disorders.