ITGB4 upregulation is associated with progression of lower grade glioma.

Gliomas originating in the neuroepithelium account for about 80% of brain malignancies and are the most common cancer of the central nervous system. Clinical management of gliomas remains challenging despite significant advances in comprehensive therapies, including radiotherapy, chemotherapy, and surgery. The ITGB4 (Integrin subunit beta 4) gene encodes a receptor for laminins and its upregulation in tumor tissues is associated with poor prognosis. However, its role in glioma is not well understood. First, we performed a pan cancer analysis of ITGB4 expression in The Cancer Genome Atlas (TCGA) dataset. Survival analysis was done on Chinese Glioma Genome Atlas (CGGA) and TCGA. Immunohistochemistry was then used to validate the expression and role of ITGB4 in glioma. We finally analyzed the possible mechanism by immune infiltration and single-cell sequencing analysis. Here, we found that ITGB4 is upregulated in glioma and accurately predicts the prognosis of lower grade glioma (LGG). Univariate and multivariate Cox regression analyses showed that ITGB4 is a risk factor for LGG. Immunohistochemical analysis confirmed that ITGB4 accurately predicts LGG prognosis. Non-negative matrix factorization (NMF) cluster analysis showed that ITGB4 was closely related to immune related genes. Immune cell infiltration and single cell sequencing analyses indicated that ITGB4 may be closely related to the microenvironment of gliomas, especially tumor-associated fibroblasts. ITGB4 is a promising diagnostic and therapeutic factor in LGG patients.

Polydatin alleviates severe traumatic brain injury induced acute lung injury by inhibiting S100B mediated NETs formation.

Severe traumatic brain injury (sTBI)-induced acute lung injury (sTBI-ALI) is regarded as the most common complication of sTBI that is an independent predictor of poor outcomes in patients with sTBI and strongly increases sTBI mortality. Polydatin (PD) has been shown to have a potential therapeutic effect on sTBI-induced neurons injury and sepsis-induced acute lung injury (ALI), therefore, it is reasonable to believe that PD has a protective effect on sTBI-ALI. Here, to clarify the PD protective effect following sTBI-ALI, a rat brain injury model of lateral fluid percussion was established to mimic sTBI. As a result, sTBI induced ALI, and caused an increasing of wet/dry weight ratio and lung vascular permeability, as well as sTBI promoted oxidative stress response in the lung; sTBI caused inflammatory cytokines release, such as IL-6, IL-1ß, TNF-α and MCP-1; and sTBI promoted NETs formation, mainly including an increasing expression of MPO, NE and CitH3. Simultaneously, sTBI induced a significant increase in the level of S100B; however, when inhibition of S100B, the expression of MPO, NE and CITH3 were significantly inhibited following sTBI. Inhibition of S100B also promoted lung vascular permeability recovery and alleviated oxidative stress response. Furthermore, PD treatmentreduced the pathological lung damage, promoted lung vascular permeability recovery, alleviated oxidative stress response and inflammatory cytokines release; more importantly, PD inhibited the expression of S100B, and NETs formation in the lung following sTBI. These results indicate that PD alleviates sTBI-ALI by inhibiting S100B mediated NETs formation. Thus, PD may be valuable in sTBI-ALI treatment.

A novel surgical technique for spontaneous intracerebral hematoma evacuation.

Stereotactic removal of intracerebral hematoma is a routine procedure for treating hypertensive intracerebral hemorrhage, but the complex sequence of operations limits its adoption. We explored the application of a novel surgical technique for the removal of spontaneous intracerebral hematomas. The surgical technique based on computed tomography (CT) images was used in hematoma projection and surgical planning. Markers placed on the scalp based on an Android smartphone app allowed the installation of a stereotactic head frame to facilitate the selection of the best trajectory to the hematoma center for removing the hematoma. Forty-two patients with spontaneous intracerebral hemorrhage were included in the study, including 33 cases of supratentorial hemorrhage, 5 cases of cerebellum hemorrhage, and 4 cases of brain stem hemorrhage. The surgical technique combined with the stereotactic head frame helped the tip of the drainage tube achieve the desired position. The median surgical time was 45 (range 25-75) min. The actual head frame operating time was 10 (range 5-15) min. Target alignment performed by the surgical technique was accurate to ≤ 10.0 mm in all 42 cases. No patient experienced postoperative rebleeding. In 33 cases of supratentorial intracerebral hemorrhage, an average evacuation rate of 77.5% was achieved at postoperative 3.1 ± 1.4 days, and 29 (87.9%) cases had a residual hematoma of < 15 ml. The novel surgical technique helped to quickly and effortlessly localize hematomas and achieve satisfactory hematoma removal. Clinical application of the stereotactic head frame was feasible for intracerebral hemorrhage in various locations.

Bibliometric Analysis of ATAC-Seq and Its Use in Cancer Biology via Nucleic Acid Detection.

Assay for transposase-accessible chromatin using sequencing (ATAC-seq) is associated with significant progress in biological research and has attracted increasing attention. However, the impact of ATAC-seq on cancer biology has not been objectively analyzed. We categorized 440 ATAC-seq publications according to the publication date, type, field, and country. R 3.6.2 was used to analyze the distribution of research fields. VOSviewer was used for country co-authorship and author co-authorship analyses, and GraphPad Prism 8 was used for correlation analyses of the factors that may affect the number of articles published in different countries. We found that ATAC-seq plays roles in carcinogenesis, anticancer immunity, targeted therapy, and metastasis risk predictions and is most frequently used in studies of leukemia among all types of cancer. We found a significantly strong correlation between the top 10 countries in terms of the number of publications and the gross expenditure on research and development (R&D), the number of universities, and the number of researchers. At present, ATAC-seq technology is undergoing a period of rapid development, making it inseparable from the emphasis and investment in scientific research by many countries. Collectively, ATAC-seq has advantages in the study of the cancer mechanisms because it can detect nucleic acids and thus has good application prospects in the field of cancer, especially in leukemia studies. As a country's economic strength increases and the emphasis on scientific research deepens, ATAC-seq will definitely play a more significant role in the field of cancer biology.

[Application of the "five-line division method" in selecting surgical approach for spaceoccupying lesions in the saddle area and the adjacent areas].

OBJECTIVE: To explore the application of the"five-line division method "in selecting the surgical approach for occupying lesions in the saddle area and its adjacent areas. METHODS: Based on the natural anatomic structures, 5 lines (alpha, beta, theta line and lambda, epsilon line) were drawn on the images of the craniocerebral axial plane crossing the middle of the saddle area and the craniocerebral median sagittal plane, thus dividing the saddle area and its adjacent areas into 6 regions in the axial plane (1, 2, 3, 1', 2', and 3' regions) and into 4 regions in the sagittal plane (I, II, III, and IV regions). Based on these divisions, the large space-occupying lesions in the saddle area and adjacent areas were classified and their respective surgical approaches were determined after reviewing the commonly used approaches in the saddle area and clinical experiences. We collected the data of 116 patients undergoing surgeries for space-occupying lesions involving the saddle and the adjacent areas in our hospital between September, 2014 and August, 2017, and analyzed their classifications and the corresponding surgical approaches based on the "five- line division method " to compare the consistency between the hypothetic approaches and the approaches adopted in the actual surgeries. RESULTS: The actual surgical approaches adopted in the 116 cases were all selected under the guidance of experts in our hospital. The hypothetic surgical approaches selected based on the"five- line division method "showed a good consistency with the actually adopted approaches. CONCLUSIONS: The"five-line division method "can spatially classify the commonly seen space-occupying lesions involving the saddle area and its adjacent area to provide assistance in the selection of surgical approaches for such lesions.

Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria.

Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intraperitoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial superoxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane potential was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 expression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway. This study was approved by the Animal Care and Use Committee of the Southern Medical University, China (approval number: L2016113) on January 1, 2016.

Association of astragaloside IV-inhibited autophagy and mineralization in vascular smooth muscle cells with lncRNA H19 and DUSP5-mediated ERK signaling.

Defective autophagy in vascular smooth muscle cells (VSMCs) is the principal cause of atherosclerosis. This study aimed to investigate the effect of astragaloside IV (AS-IV) on VSMCs autophagy. In vivo, ApoE-/- mice were fed with high-fat diet ad libitum for eight weeks, with or without AS-IV (25 mg/kg, daily). In vitro, human VSMCs were cultured and treated with ß-Glycerophosphate (10 mmol/L) and AS-IV (50 µg/ml). VSMCs autophagy, mineralization, expression of p-ERK1/2, p-mTOR, and autophagy-related proteins (LC3 II/I, p62, and Beclin 1) were detected. Increased autophagy and mineralization was observed in VSMCs in thoracic aorta of mice and in in vitro VSMCs model of atherosclerosis. AS-IV administration attenuated the autophagy and mineralization in VSMCs. Reverse expression profiles of H19 and DUSP5 were observed. AS-IV inhibited DUSP5 and autophagy-related proteins and increased expression of H19, level of p-ERK1/2 and p-mTOR. Further, autophagy and mineralization level in VSMCs were in line with DUSP5 expression level, but in contrast to H19, p-ERK1/2, and p-mTOR profiles. We demonstrated that AS-IV could attenuate autophagy and mineralization of VSMCs in atherosclerosis, which may be associated with H19 overexpression and DUSP5 inhibition.

[Efficacy of inactivated autologous porous bone flap and BAM bone-induced artificial bone for repairing skull defect in rats].

OBJECTIVE: To study the effect of BAM bone grafting combined with inactivated autologous porous bone flap in repairing skull defect in rats. METHODS: Seventy-two Wistar rats with skull defect were randomly divided into control group, inactivated autologous bone flap group (AB group), BAM bone-induced artificial bone material group (BAM group), and inactivated autologous bone flap with BAM bone-induced artificial bone group (BAM+AB group). The bone healing was evaluated with micro-CT and the new bone formation was assessed with histological staining at 1, 2, and 3 months after modeling. RESULTS: Inactivated porous bone flap combined with BAM bone-induced artificial bone effectively induced vascular and fibrous tissue regeneration and osteogenesis in the cranial defects. With the inactivated porous bone flap as the scaffold, BAM bone-induced artificial bone obviously promoted the restoration of the skull appearance in the rats with cranial defects. CONCLUSION: Inactivated autologous bone flap group and BAM bone-induced artificial bone material can promote skull healing and restoration of the original skull appearance, and can be used for reconstruction of the local anatomy of the skull surface.

Puerarin ameliorated the behavioral deficits induced by chronic stress in rats.

The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.

Surgical management of radiation-induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: report of 14 cases.

BACKGROUND: Radiation-induced temporal lobe necrosis is a rare and serious late complication in irradiated patients with nasopharyngeal carcinoma (NPC). Treatment of radiation-induced temporal lobe necrosis with surgery has been seldom thoroughly investigated. METHODS: We retrospectively analyzed the clinical data of 14 patients with radiation-induced temporal lobe necrosis treated with surgical intervention. RESULTS: Radiation-induced temporal lobe necrosis presented as obvious cystic formation or as heterogeneous enhanced nodule on MRI. Among 3 patients with (18)F-fluorodeoxyglucose ((18)F-FDG) PET-CT scan, increased uptake of (18)F-FDG was observed in 2 cases. Four patients were anesthestized nasotracheally and 1 was through tracheostomy during surgery because of other radiation complications, including trismus and skull base osteoradionecrosis. The temporal approach was applied in all cases, with the removal of bone flap in 11 patients. During follow-up, 1 patient died of exhaustion. CONCLUSIONS: Surgery benefits selected patients with NPC with radiation-induced temporal lobe necrosis. The goals of surgery are to relieve the increased intracranial pressure and to establish the accurate diagnosis.

[Three-dimensional white matter tractography based on diffusion-tensor magnetic resonance imaging].

OBJECTIVE: To assess the value of white matter fiber tractography based on magnetic resonance diffusion-tensor imaging (MR-DTI), a new noninvasive technique that helps estimate the structural connectivity of the brain, in understanding the anatomy of the white matter fiber tract. METHODS: Six consecutive volunteers received MR-DTI examination using a GE 1.5T Sign CV/I whole-body MR system and version 2.0 Functool software for image processing. The protocol included T1WI for localization and single-shot echo-planner diffusion tensor imaging of the entire brain in axial, sagittal, and /or coronal sections. RESULTS: White matter fiber tracts imaged by MR-DTI were consistent with known white matter fiber anatomy. The major fiber tracts were well observed in all the cases. The tracts visualized included the corpus callosum, anterior commissure, uncinate fasciculus superior and inferior longitudinal fascicules, inferior occipito-frontal fasciculus, internal capsule and corona radiate. CONCLUSION: A set of detailed white matter fiber anatomy maps of the normal brain is obtained by means of single-shot echo-planner diffusion tensor imaging at high resolution. This technique allows rapid visualization of the white matter tracts in vivo, and provides a new reliable means for studying fiber connectivity in the brain.

[Diffusion tensor imaging of the white matter tracts in preoperative patients with cerebral neoplasm].

OBJECTIVE: To evaluate the quantitative relationship between white matter tract (WMT) variation resulting from cerebral tumors and shifting of the fractional anisotropy (FA) index in magnetic resonance (MR) diffusion tensor imaging (DTI). METHODS: Four female and 8 male patients aged from 21 to 62 years with brain malignancies (2 malignant lymphomas, 2 low-grade astrocytomas, and 8 high-grade cerebral gliomas) underwent conventional contrast-enhanced MR and DTI examinations before operation. Routine T(2)-weighted image, fractional anisotropic (FA) map, color-coded directional map, three-dimensional white matter tractography (WMT), and the FA index of bilateral internal capsule were obtained in every patient. RESULTS: Fiber tractography derived from DTI was consistent with known white matter fiber anatomy. The DTI patterns in WMT altered by the tumor were categorized on the basis of FA1/FA2 ratio as follows: pattern 1, FA1/FA2> or =75% with normal or only slightly decreased FA; pattern 2, 50%< or =FA1/FA2<75% with WMT displacement; pattern 3, 25%< or =FA1/FA2/50% with WMT involvement; pattern 4, FA1/FA2<25% with WMT destruction. CONCLUSIONS: DTI allows for visualization of WMT and benefits surgical planning for patients with intrinsic brain tumor. There is a positive relationship between the bilateral FA ratio (FA1/FA2) variation and WMT alterations resulting from the tumor.