Differentiation profile of brain tumor stem cells:a comparative study with neural stem cells

Understanding of the differentiation profile of brain tumor stem cells （BTSCs）, the key ones among tumor cell population, through comparison with neural stem cells （NSCs） would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD 133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and β-tubulinlII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma.

The Expression of Estrogen Receptor Subtypes in Prolactinomas and Their Relationship to Tumor Biological Behavior

Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors （ER） in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,

A case of malignant fibrous histiocytoma of the head after trauma and radiation therapy

Malignant fibrous histiocytoma(MFH) firstly described as"malignant fibrous xanthoma"by O' Brien and Stout in 1964, is the most common soft tissue sarcoma of late adult life.Uncertain histogenesis and numerous subtypes make MFH a rather controversial entity.MFH only rare arises from structures of the head and neck.When it does, it most often originates in facial structures, particularly the maxilla.This report details a case of a patient with malignant fibrous histiocytoma presenting clinically as a right-sided large indurated frontoparietal mass, three months after head trauma and eight years after radiation therapy for brain lymphoma located in the right frontal and parietal lobes.Radical excision was a surgical challenge because of the extensiveness of the lesion.

The Outcome of Endoscopic Third Ventriculostomy in a Mixed Population of Adult and Pediatric Patients

Background: Endoscopic third ventriculocisternostomy (ETV) is the most common neuroendoscopic technique in the treatment of noncommunicating hydrocephalus. Since its introduction, ETV has been a safe alternative to ventriculoperitoneal shunt (VP shunt), which has a high complication rate with significant socio-economic consequences. The authors report the results of ETV performed in the neurosurgical department of FANN teaching hospital in Dakar. Methods: This retrospective study presents the results of ETV performed in 513 patients with hydrocephalus of various etiologies, ranging from February 2010 to February 2018. We have included in our series from 2010 to 2016, all patients with clinically revealed non-communicating hydrocephalus followed by a brain computed tomography (CT) scan or brain magnetic resonance imaging (MRI) and who have benefited from an ETV, in which the ETV Success Score was evaluated. Results: The mean age of our patients was 14.10 years, with 298 (58%) males. The clinical symptomatology varied in both children and adults and manifested in children as macrocrania in 67.8% of the patients, while in adults, it manifested as raised intracranial pressure (ICP) in 87.5% of patients. A brain CT scan was performed in 461 (89.86%) of patients. The causes of hydrocephalus were dominated in 49% of patients by malformative pathologies, followed by tumors in 41% of patients, infections in 2.33% of patients, and normal-pressure hydrocephalus in 3.8% of patients. During the postoperative period, we found 21.41% of various complications. Conclusions: The findings in our series were compared to those in the literature and were satisfactory, thus proving the effectiveness and safety of ventriculocisternostomy in our department. In resource-limited countries, ETV can be performed with good results and less mortality and morbidity.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the develop-ment of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133＋and CD133？ cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7–11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133＋ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133？ cell suspension, and Notch-immunopositive expres-sion was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133＋ astro-cytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However,it should be emphasized that the sub-cortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133？ astrocytoma cells. However, these ifndings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treat-ment target for diffuse spinal cord astrocytoma.

Tissue plasminogen activator via cross-collateralization for tandem internal carotid and middle cerebral artery occlusion

Tandem internal carotid and middle cerebral artery occlusion after carotid dissection predicts poor outcome after systemic thrombolysis. Current treatments include the use of endovascular carotid stenting, which carries with it a high risk of propagating further embolic events and worsening the dissection. New strategies for avoiding the aforementioned side-effects include recanalization using cross-collaterals for delivery of intra-lesional tissue plasminogen activator(t PA). We present two cases that provide further support for this novel approach. Both patients presented with a National Institute of Health Stroke Scale of 20, received intra-arterial t PA via cross-collateralization, and made full recoveries without the need for stenting.

Clinical features,radiological profiles,pathological features and surgical outcomes of pituicytomas:a report of 11 cases and a pooled analysis of individual patient data

Background:Pituicytoma is an extremely rare low-grade glial tumor that is closely related to the neurohypophysis axis.Most studies of pituicytomas include only several cases.To better understand this disease,we reviewed a series of cases of pituicytomas.The diagnosis and treatment of pituicytoma must be further elucidated.Methods:Eleven patients with pituicytoma admitted to Beijing Tiantan Hospital from 2012 to 2019 were selected.The clinical features,including radiological and histological examination,surgical records and prognosis were reviewed.Sixty-eight other previously published cases of pituicytoma also were used to analyze the predictive factors for the results.The Cox regression model was used for univariate and multivariate analyses.Results:Our patients included 5 males(45.5%)and 6 females(54.5%),with a mean age of 49.3 years.The tumor was located in the suprasellar region in 5 patients(45.5%),intrasellar region in 4 patients(36.4%),and intrasellarsuprasellar region in 2 patients(18.2%).All patients were misdiagnosed with other common tumors in the sellar region before the operation.During the operation,gross total resection(GTR)of the tumor was achieved in 6 patients(54.5%),and subtotal resection(STR)was achieved in 5 patients(45.5%).The mean progression-free survival(PFS)time was 29.82 months.Tumor progression after surgical resection occurred in 4 patients(36.4%).Among them,60.0%of the patients(cases 4,5,7)with STR experienced progression,while 16.7%of the patients(case 2)with GTR experienced progression.Combined with the 68 cases in the literature,GTR was an independent risk factor for PFS time(P<0.05).Conclusions:Pituicytomas are more common in middle-aged people and the sellar region.The clinical manifestations of pituicytomas are different,but no diagnostic clinical features have been identified other than an abnormally abundant blood supply.Currently,GTR is the best approach for the treatment of pituicytomas.More patients and longer follow-up periods were needed to further elucidate the biological features of pituicytomas.

Benign Fibrous Histiocytoma of the Neurocranium

Presented is a case of benign fibrous histiocytoma (BFH) involving the calvarium of a 25 years old lady who noticed a depression in her occiput associated with localised pain. Imaging revealed a tumour eroding through the inner and outer skull tables, closely associated with major underlying dural sinuses. She underwent complete macroscopic resection of the tumour and reconstruction of a titanium mesh cranioplasty. Histology favoured a benign process with a diagnosis of BFH of the calvarium given. At 1 year follow-up, the patient is asymptomatic and has not developed recurrence of the tumour.

Total En Bloc Spondylectomy for Lumbar Renal Cell Carcinoma and Review of the Literature

Introduction: Total en bloc spondylectomy (TES) is gaining increasing favour as a treatment of choice for cancers of the spine that are resistant to radiological and chemotherapeautic intervention such as renal cell carcinoma (RCC). Until recently, RCC of the lumbar spine has presented a surgical challenge due to anatomical and vascular constraints. The development of the combined posterior-anterior en bloc spondylectomy offers improved access to the lumbar region. This case report and review of the literature presents a combined posterior-anterior lumbar en bloc spondylectomy for RCC involving L3 vertebra, which we believe is the first reported in Australia. Methods: A 46-year-old male with a seven-year history of renal cell carcinoma resulting in a left nephrectomy presented with a lytic lesion involving the L3 vertebral body, extending to the epidural space and compressing the cauda equina and left L3 and L4 nerve roots on MRI. A literature review revealed ten previous cases of the posterior-anterior TES in the lumbar spine for cancerous lesions but none from Australia. Results: A posterior-anterior TES and L2-L4 fusion was performed to remove a cancerous renal cell carcinoma of L3 with wide margins. Blood loss was the major complication. The patient remains recurrence free at nineteen months post procedure. Conclusion: Despite being an aggressive and invasive procedure, TES is rapidly becoming the treatment of choice for curative and palliative care in select patients with isolated metastatic tumours of the lumbar spine.

Application of robotic-assisted endoscopic third ventriculostomy

Objective:This case series study explored the application of ROSA(robot of stereotactic assistant)robotic-assisted endoscopic third ventriculostomy(ETV)in the treatment of hydrocephalus.Methods:Three patients(January2016-October2017)diagnosed with hydrocephalus based on preoperative computed tomograph(CT)and magnetic resonance imaging(MRI)scans were recruited.Navigation planning scan was performed before operation.ROSA robot localization program was used to simulate and analyze the path planning of hydrocephalus ETV and store it in the system.All the three patients underwent robotic-assisted ETV.The patients'clinical symptoms,imaging manifestations and related complications were evaluated,and a3-month follow-up survey was conducted.Prognostic factors were also analyzed.Results:ETV under the guidance of ROSA robot was successfully performed on the three patients.CT,MRI and cerebrospinal fluid(CSF)cine showed that the ventricles were narrowed,that the velocity and flow of the stoma were normal,and that the CSF flow was smooth.After discharge,the symptoms of hydrocephalus were significantly improved.Localization of the robot and design of the surgical path were key to success of the operation.Conclusions:ROSA robotic-assisted ETV is a feasible procedure.The patients recovered well,and the symptoms relieved.More efforts are needed to optimize artificial intelligence and the application of precision treatment in the nervous system.

Discogenic pain: Who cares?

Chronic low back pain has a huge impact on daily living and a negative economic and professional effect. It is a matter of debate and concern for all health professionals involved, particularly spine surgeons. Recent discoveries on the innervation and biochemical properties of the intervertebral disc clarify the role of this structure as a possible cause of chronic low back pain. However, multiple causes may be present in the same patient making the diagnosis a challenging process. Discogenic pain is defined as a chronic low back pain induced by a degenerative disc disease. There are no specific characteristics of discogenic pain, although it has a higher incidence in younger age, it is usually localized medially in the back, worsens with axial loading and improves with recumbence. In the last decades we have assisted the emergence of multiple treatment techniques. However, neither the conservative treatment nor the interventional management has strong evidence in treating discogenic pain. Randomized control clinical trials are sought to improve patient outcome. Meanwhile, we believe each patient should be approached on an individual base. Discogenic pain: we care.

RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells.Relevant studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of therapeutics.As a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular phenotypes.To be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts.In this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied types.Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial metabolism.And we highlight the regulation of RNA modifications on immunometabolism,further influencing immune responses.Above all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted therapeutics.Eventually,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

Intracranial pressure monitoring for special patterns of frontal lobe contusions

Objective： To study the effect and indications ofintracranial pressure （ICP） monitoring for frontal lobe contusion patients. Methods： During January 2005-December 2008, 34 cases of frontal lobe contusion received ICP monitoring in our department （monitoring group）. Different treatment protocols were adopted according to the results of ICP. Mean-while 46 cases of same type of head-injured patients who did not undergo ICP monitoring served as control group. Results： We found that ICP elevated dramatically within 24 hours after head injury if the contusions were located in frontal longitudinal dehiscence, bilateral undersurface of frontal lobe or dispersed in bilateral lobe. After half a year follow-up and on the basis of Glasgow Coma Scale assessment, the monitoring group showed better outcome than the control group with good recovery in 24 cases （70.6%）, moderate disability in 7 cases （20.6%）, severe disability in 2 （5.88%） and death in 1 （2.94%）. The outcome of control group displayed good condition in 25 cases （54.3%）, moderate disabilities in 8 （17.4%）, severe disability in 7 （15.2%）, and death in 6 （13.0%）. Conclusions： Frontal lobe contusions are vulnerable and complex head injuries, especially when the contusions are located in frontal longitudinal dehiscence, bilateral undersurface of frontal lobe or diffused in bilateral lobes. These patients should undergo ICP monitoring regardless of their consciousness status. IflCP elevates over 25 mm Hg, the craniotomy is mandatory and will markedly reduce the mortality and disability of these patients.

Deep brain stimulation in the treatment of tardive dystonia

Dystonia refers to a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures. Secondary dystonia is associated with acquired or exogenous causes, hereditary neurologic syndromes or neurodegenerative disorders. Tardive dystonia is a special type of secondary dystonia due to exposure to certain medicines such as neuroleptics, with a chronic and persistent extrapyramidal symptoms.

Endoscopy-assisted cerebral falx incision via unilateral approach for treatment of dissymmetric bilateral frontal contusion

Objective： To investigate the clinical features and treatment strategy of dissymmetric bilateral frontal contusion, and to summarize our experience in treating these patients by minimally invasive surgery. Methods： Over the past 3 years, we have treated a total of 31 patients with dissymmetric bilateral frontal contusion using endoscopy-assisted unilateral cerebral falx incision. ~ ~ther 30 patients treated by routine bilateral approaches within the same period were taken as control. Results： Seventeen cases （54.8%） in the unilateral operation group survived and were in good condition, 8 （25.8%） had moderate disability, 4 （12.9%） had severe disability, 1 （3.2%） was in vegetative state, and 1 （3.2%） died. Compared with the control group, the Glasgow Out- come Scale score was not significantly different in the uni-lateral operation group, but the operation time, blood trans- fusion volume, the length of hospital stay, the incidences of mental disorder and olfactory nerve injury were greatly reduced in the unilateral operation group. Conclusions： Endoscopy-assisted unilateral cerebral falx incision can shorten the operation time, reduce surgical trauma and complications in treatment of patients with dissymmetric bilateral frontal contusion. It can obviously diminish the chance of delayed intracerebral hematoma and subsequently minimize the incidences of subfalcial and centrencephalic herniation.

White Matter Deficits Underlying the Impaired Consciousness Level in Patients with Disorders of Consciousness

In this study, we aimed to （1） identify white matter （WM） deficits underlying the consciousness level in patients with disorders of consciousness （DOCs） using diffusion tensor imaging （DTI）, and （2） evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/ vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest （ROIs）, and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients.

Differential gene expression by fiber-optic beadarray and pathway in adrenocorticotrophin-secreting pituitary adenomas

Background Adrenocorticotrophin （ACTH）-secreting pituitary adenomas account for approximately 7%-14% of all pituitary adenomas, but its pathogenesis is still enigmatic. This study aimed to explore mechanisms underlying the pathogenesis of ACTH-secreting pituitary adenomas.Methods We used fiber-optic beadarray to examine gene expression in three ACTH-secreting adenomas compared with three normal pituitaries. Four differentially expressed genes from the three ACTH-secreting adenomas and three normal pituitaries were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction （RT-qPCR）. We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway.Results Fiber-optic beadarray analysis showed that the expression of 28 genes and 8 expressed sequence tags （ESTs）were significantly increased and the expression of 412 genes and 31 ESTs were significantly decreased. Bioinformatic and pathway analysis showed that the genes HIGD1B, EPS8, HPGD, DAPK2, and IGFBP3 and the transforming growth factor （TGF）-β signaling pathway and extracellular matrix （ECM）-receptor interaction pathway may play important roles in tumorigenesis and progression of ACTH-secreting pituitary adenomas.Conclusions Our data suggest that numerous aberrantly expressed genes and several pathways are involved in the pathogenesis of ACTH-secreting pituitary adenomas. Fiber-optic beadarray combined with pathway analysis of differential gene expression appears to be a valid method of investigating tumour pathogenesis.

Integrating Au and ZnO nanoparticles onto graphene nanosheet for enhanced sonodynamic therapy

Sonodynamic therapy has attracted widespread attention for cancer treatment because of its noninvasiveness and high tissuepenetration ability.Generally,ultrasound irradiation of sonosensitizers produces separated electrons(e−)and holes(h+),which inhibits cancer by producing reactive oxygen species(ROS).However,the separated electrons(e−)and holes(h+)could easily recombine,lowering the yield of ROS and hindering the application of sonodynamic therapy(SDT).Herein,we present a highly efficient sonosensitizer system for enhanced sonodynamic therapy built on reduced graphene oxide(rGO)nanosheets,bridged ZnO and Au nanoparticles,coated with polyvinyl pyrrolidone(PVP).The ultrasound irradiation activates ZnO nanoparticles to generate separated electron–hole(e−–h+)pairs,and the rGO nanosheets facilitate electron transfer from ZnO to Au nanoparticles because of the narrow band gap of rGO,which could efficiently restrain the recombination of the e−–h+pairs,thereby significantly augmenting the production of ROS to kill cancer cells,such as U373MG,HeLa,and CT26 cells.Moreover,rGO nanosheets integrated with Au nanoparticles could catalyze the endogenous decomposition of H_(2)O_(2) into O_(2),which can alleviate hypoxic tumor microenvironment(TME).Therefore,the rational design of Au-rGO-ZnO@PVP nanomaterials can not only improve the efficiency of sonodynamic therapy,but also mitigate the hypoxic tumor microenvironment,which would provide a new perspective in the development of efficient sonosensitizers.

Eye-Opening Alters the Interaction Between the Salience Network and the Default-Mode Network

Dear Editor,Brain networks consist of several long-distance regions that interact constantly with each other.Interactions between networks suggest that different brain functions are coordinated during complex cognitive tasks[1].A triple-network mechanism underlying cognitive control has been found across task paradigms and stimulus modalities[2].This triple-network mechanism includes the interactions among the salience network(SN),the default mode network(DMN),and the central executive network(CEN).

Zero drift of intraventricular and subdural intracranial pressure monitoring systems

Objective： To assess zero drift of intra- ventricular and subdural intracranial pressure （ICP） moni- toring systems. Methods： A prospective study was conducted in pa- tients who received Codman ICP monitoring in the neuro- surgical department from January 2010 to December 2011. According to the location of sensors, the patients were ca- tegorized into two groups： intraventricular group and sub- dural group. Zero drift between the two groups and its as- sociation with the duration of ICP monitor were analyzed. Results： Totally, 22 patients undergoing intraven- tricular ICP monitoring and 27 receiving subdural ICP moni- toring were enrolled. There was no significant difference in duration of ICP monitoring, zero drift value and its absolute value between intraventricular and subdural groups （5.38 d± 2.58 d vs 4.58 d.±2.24 d, 0.77 mmHg±2.18 mmHg vs 1.03 mmHg±2.06mmHg, 1.68 mmHg~.l.55 mmHgvs 1.70mmHg.t_l.53 mmHg, respectively; all P〉0.05）. Absolute value of zero drift in both groups significantly rose with the increased duration of ICP monitoring （P〈0.05） while zero drift value did not. Moreover, daily absolute value in the intraventricular group was sig- nificantly smaller than that in the subdural group （0.27 mm Hg_＋ 0.32 mm Hg vs 0.29 mm Hg_-_＊0.18 mm Hg, P〈0.05）. Conclusion： This study demonstrates that absolute value of zero drift significantly correlates with duration of both intraventricular and subdural ICP monitoring. Due to the smaller daily absolute value, ICP values recorded from intraventficular system may be more reliable than those from subdural system.