Unveiling novel cell clusters and biomarkers in glioblastoma and its peritumoral microenvironment at the single-cell perspective.

BACKGROUND: Glioblastoma (GBM) is a highly heterogeneous, recurrent and aggressively invasive primary malignant brain tumor. The heterogeneity of GBM results in poor targeted therapy. Therefore, the aim of this study is to depict the cellular landscape of GBM and its peritumor from a single-cell perspective. Discovering new cell subtypes and biomarkers, and providing a theoretical basis for precision therapy. METHODS: We collected 8 tissue samples from 4 GBM patients to perform 10 × single-cell transcriptome sequencing. Quality control and filtering of data by Seurat package for clustering. Inferring copy number variations to identify malignant cells via the infercnv package. Functional enrichment analysis was performed by GSVA and clusterProfiler packages. STRING database and Cytoscape software were used to construct protein interaction networks. Inferring transcription factors by pySCENIC. Building cell differentiation trajectories via the monocle package. To infer intercellular communication networks by CellPhoneDB software. RESULTS: We observed that the tumor microenvironment (TME) varies among different locations and different GBM patients. We identified a proliferative cluster of oligodendrocytes with high expression of mitochondrial genes. We also identified two clusters of myeloid cells, one primarily located in the peritumor exhibiting an M1 phenotype with elevated TNFAIP8L3 expression, and another in the tumor and peritumor showing a proliferative tendency towards an M2 phenotype with increased DTL expression. We identified XIST, KCNH7, SYT1 and DIAPH3 as potential factors associated with the proliferation of malignant cells in GBM. CONCLUSIONS: These biomarkers and cell clusters we discovered may serve as targets for treatment. Targeted drugs developed against these biomarkers and cell clusters may enhance treatment efficacy, optimize immune therapy strategies, and improve the response rates of GBM patients to immunotherapy. Our findings provide a theoretical basis for the development of individualized treatment and precision medicine for GBM, which may be used to improve the survival of GBM patients.

Mechanistic insight into glioma through spatially multidimensional proteomics.

Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.

Telmisartan inhibits microglia-induced neurotoxic A1 astrocyte conversion via PPARγ-mediated NF-κB/p65 degradation.

Astrocytes are crucially involved in neuroinflammation. Activated astrocytes exhibit at least two phenotypes, A1 (neurotoxic) and A2 (neuroprotective). The A1 phenotype is the major reactive astrocyte phenotype involved in aging and neurodegenerative diseases. Telmisartan, which is an antihypertensive agent, is a promising neuroprotective agent. This study aimed to investigate the effects of telmisartan on the phenotype of reactive astrocytes. Astrocytes were activated by culturing with the conditioned medium derived from lipopolysaccharide-stimulated microglia. This conditioned medium induced early, transient A2 astrocyte conversion (within 24 h) and late, sustained A1 conversion (beginning at 24 h and lasting up to 7 days), with a concomitant increase in the production of pro-inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor [TNF]α, and IL-6) and phosphorylation of nuclear factor-κB (NF-κB)/p65. Telmisartan treatment promoted and inhibited A2 and A1 conversion, respectively. Telmisartan reduced total and phosphorylated p65 protein levels. Losartan, a specific angiotensin II type-1 receptor (AT1R) blocker, did not influence the reactive state of astrocytes. Additionally, AT1R activation by angiotensin II did not induce the expression of pro-inflammatory cytokines and A1/A2 markers, indicating that the AT1R signaling pathway is not involved in the astrocyte-mediated inflammatory response. A peroxisome proliferator-activated receptor γ (PPARγ) antagonist reversed the effects of telmisartan. Moreover, telmisartan-induced p65 downregulation was reversed by the proteasome inhibitor MG132. These results indicate that telmisartan suppresses activated microglia-induced neurotoxic A1 astrocyte conversion through p65 degradation. Our findings contribute towards the elucidation of the anti-inflammatory activity of telmisartan in brain disorders.

Meningioangiomatosis Combined with Calcifying Pseudoneoplasms of Neuraxis.

Meningioangiomatosis (MA) is a rare hamartomatous or meningovascular lesion involving the central nervous system, and is sometimes associated with intracranial meningiomas. Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing benign tumor-like lesions that can occur anywhere along the neuraxis. Here, we report a rare case of MA combined with CAPNON. A 31-year-old woman was admitted to our hospital because of a high-density mass in the left frontal lobe, detected by computed tomography (CT) during a physical examination. She had a 3-year history of obsessive-compulsive disorder. We describe the imaging, histopathological, and molecular characteristics of the patient. To our knowledge, this is the first report describing MA combined with CAPNON. We reviewed the literature on MA and CAPNON over the last decade and summarized the points for differential diagnosis and treatment. It is difficult to preoperatively distinguish between MA and CAPNON. However, this coexisting condition should be considered when intra-axial calcification lesions are observed on radiological imaging. Accurate diagnosis and appropriate treatment are likely to benefit this patient group.

Development and Validation of a Deep Learning Predictive Model Combining Clinical and Radiomic Features for Short-Term Postoperative Facial Nerve Function in Acoustic Neuroma Patients.

OBJECTIVE: This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging (MRI) for short-term postoperative facial nerve function in patients with acoustic neuroma. METHODS: A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included. Clinical data and raw features from four MRI sequences (T1-weighted, T2-weighted, T1-weighted contrast enhancement, and T2-weighted-Flair images) were analyzed. Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features. Nomogram, machine learning, and convolutional neural network (CNN) models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate model performance. A total of 1050 radiomic parameters were extracted, from which 13 radiomic and 3 clinical features were selected. RESULTS: The CNN model performed best among all prediction models in the test set with an area under the curve (AUC) of 0.89 (95% CI, 0.84-0.91). CONCLUSION: CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma. As such, CNN modeling may serve as a potential decision-making tool for neurosurgery.

A new neurosurgical adjustable pressure suction apparatus with a mechanically controlled air inlet: the study of precise regulation and atraumatic suction.

Background: An essential surgical tool in neurosurgery is the suction tube. The skillful and accurate use of a suction tube facilitates the neurosurgical operation. Objective: This study is to verify the practicality of an adjustable pressure suction tube (APS tube) and to explore the ideal APS tube diameter and tip negative pressure for different intracranial structures. Methods: APS tubes were used to aspirate brain tissues and carotid arteries of rats. Laser speckle contrast imaging (LSCI) was used to record the blood flow velocity (BFV). We measured APS tube diameter, air inlet size, tip negative pressure and central negative pressure and calculated the correlation between them. In our department, intraoperative real-time parameters including APS tube diameter, length, air inlet size, and central negative pressure were recorded, and the tube tip negative pressure suitable for different intracranial structures and parts was calculated. Results: All experiments were carried out using APS tubes. Experiments on rats objectively reflected a severe structural damage to the brain and blood vessels by the suction tube, which might even result in an irreversible reduction in blood flow., Rat carotid arteries and brain tissue suffered severe damage when the tip negative pressure exceeded 33.4 ± 1.8 and 29.2 ± 2.0 kPa, respectively. BFV failed to return to the preoperative level 3 min after the operation (p < 0.05), and this decrease was more pronounced when the suction tube diameter was large (p < 0.05). The tip negative pressure was positively and negatively correlated with central negative pressure and the air inlet size, and was independent of APS tube diameter. A total of 50 operations including 39 tumor resection operations and 11 moyamoya disease bypass operations were recorded. Large-diameter APS tubes (3.5 mm) with an closed air inlet were frequently used to maintain a greater tip negative pressure before the incision of dura mater. When important structures such as motor cortex and brainstem were involved, 1.5- or 2.0-mm-diameter APS tubes were mostly used, and an air inlet was opened up to 0.7-2.1 mm to maintain a safe tip negative pressure (7.4-27.9 kPa). Conclusion: APS tubes with a mechanical knob provide stable and precise adjustment of the tip negative pressure, avoiding excessive negative pressure that causes serious damage to the intracranial structure. And, this allows the surgeon to hold the suction tube more freely and operate at any angle with an appropriate fulcrum near the incision to achieve efficient atraumatic suction and enhance surgical safety.

How to Precisely Open the Internal Auditory Canal for Resection of Vestibular Schwannoma via the Retrosigmoid Approach.

Objective: The aim of this study was to investigate how to precisely expose the intrameatal portion of vestibular schwannomas (VSs) without damaging the labyrinth. Methods: This was a retrospective study of patients who had undergone retrosigmoid resection of a VS in our institution from April 2018 to December 2021. The patients were divided into microsurgery (MS) and navigation endoscopic-assisted (combined surgery, CS) groups and the effects of image guidance and endoscopy evaluated. The tumors in the CS group were then divided into medial and lateral types by fusion imaging and the differences between the two types analyzed. Results: Data of 84 patients were analyzed. Residual tumor was detected by postoperative MRI at the fundus of the internal auditory canal in 5 of the 31 patients in the MS group and 1 of the 53 in the CS group. The labyrinth was damaged in four patients in the MS group but was not damaged in any of the CS group patients. The CS group included 29 lateral type and 24 medial type schwannomas. Endoscopic-assisted resection of residual tumor in the IAC was performed significantly more often on medial than on lateral tumors. Conclusion: Navigation and endoscopy are useful in assisting the exposure of the intrameatal portion of VSs. Preoperative MRI/CT fusion imaging is helpful in preoperative evaluation and surgical planning in patients undergoing VS surgery. Tumors of the medial type require endoscopic assistance for resection.

Comparative efficacy analysis of ultrasound-guided quadratus lumborum block and lumbar plexus block in hip arthroscopy: a pilot prospective randomized controlled trial.

Controlled trials assessing quadratus lumborum block (QLB) for post-operative analgesia in hip surgery are scarce. This study aimed to compare ultrasound-guided QLB and lumbar plexus block (LPB) for clinical efficacy in hip arthroscopy. Patients undergoing hip arthroscopy in Beijing Jishuitan Hospital in January-June 2019 were randomized to the lumbar plexus (L) and quadratus lumborum (Q) groups (n = 25/group). After either ultrasound-guided block for 30 min, both groups were prepared for surgery after muscle strength measurement in the affected limbs. Opioid doses for patient-controlled analgesia (PCA), visual analog scale (VAS) scores in the resting and active states, upon leaving the post-anesthesia care unit (PACU), and at 2-48 h post-surgery were recorded, and post-operative complications were also recorded. Muscle strength in the affected limbs was significantly higher in the Q group compared with the L group (4.0 versus 2.0, P < 0.001). VAS scores were similar in both groups post-surgery (P > 0.05). One patient had epidural spread in the L group, with no other complications. Compared with ultrasound-guided LPB, ultrasound-guided QLB provides similar and good post-operative analgesia after hip arthroscopy, with less impact on muscle strength and fewer complications. These results should be confirmed in larger trials.

Preconditioning with Trehalose Protects the Bone Marrow-Derived Mesenchymal Stem Cells Under Oxidative Stress and Enhances the Stem Cell-Based Therapy for Cerebral Ischemic Stroke.

Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has emerged as a potential treatment for ischemic stroke. Preconditioning with pharmacological agents before cell transplantation has been shown to increase the efficiency of cell therapy. In this study, trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the neuroprotective effect of BMSCs preconditioned with Tre on cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre. Immunofluorescence staining of LC3B was performed to detect autophagy, and Western blotting for LC3, Beclin1, p-AMPK, and p-mTOR was performed. Flow cytometry and Western blotting analysis were performed to measure cell apoptosis in the presence of hydrogen peroxide (H2O2). Enzyme-linked immunosorbent assay was used to test the secretion levels of neurotrophic factors. An in vivo ischemia/reperfusion model was generated by middle cerebral artery occlusion in male Sprague Dawley rats, and Tre-preconditioned BMSCs were administered intralesionally 24 hours after ischemic injury. Histopathological examination and neurological function studies were conducted. In vitro, Tre promotes autophagy of BMSCs through the activation of the AMPK signal pathway. Tre protected BMSCs from H2O2-induced cell viability reduction and apoptosis. Moreover, Tre pretreatment increased the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor, and hepatocyte growth factor. In vivo, preconditioning with Tre could further enhance the survival of BMSCs, reduce infarct size, alleviate cell apoptosis, abate vessel decrease, and ultimately improve functional recovery. Our study indicates that Tre can enhance the survival of BMSCs under oxidative stress and enhance BMSC-based treatment of ischemia/reperfusion injury.

Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma.

AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

Recent Progress on Primary Central Nervous System Lymphoma-From Bench to Bedside.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extra-nodal lymphoma. The high relapse rate of PCNSL remains a major challenge to the hematologists, even though patients exhibit high sensitivity to the methotrexate-based chemotherapeutic regimens. Recently, the advent of Bruton's tyrosine kinase inhibitor (BTKi) and CAR T treatment has made more treatment options available to a proportion of patients. However, whether BTKi monotherapy should be given alone or in combination with conventional chemotherapy is still a clinical question. The status of CAR T therapy for PCNSLs also needs to be elucidated. In this review, we summarized the latest progress on the epidemiology, pathology, clinical manifestation, diagnosis, and treatment options for PCNSLs.

Characteristics and operation outcomes of neuro-oncology patients after COVID-19 pandemic - A case series.

BACKGROUND: COVID-19 has been spreading worldwide at hitherto unknown speed, and the treatment of neuro-oncology patients without COVID-19 has been greatly affected. METHODS: To compare the medical records and surgical results of surgical patients before and after the pandemic. We collected a total of 80 patients form April 2020 to May 2020 after pandemic and from April 2019 to May 2019 before pandemic. The patient's demographics, past medical history, comorbidities, imaging, pathology, laboratory teat, and Karnofsky Performance Score (KPS) were analyzed. RESULTS: The most common presenting symptom was intracranial hypertension and neurological deficit. Hypertension and diabetes were the most common comorbid diseases. The pre-operation KPS were 83.21 ± 15.60, 80 ± 14.77, 78.57 ± 12.83 and 74.14 ± 12.72, respectively. The post-operation KPS were 94.64 ± 8.65, 95.45 ± 6.56, 91.43 ± 10.82 and 84.21 ± 22.55, respectively. The tumor volume was larger and the midline shift distance was greater after the pandemic than before. For pathological grade, meningiomas were mostly grade I, while gliomas were mainly grade III and IV. CONCLUSION: Although affected by the COVID-19 pandemic, patients with glioma should be operated as soon as possible to obtain better surgical results, however, for patients with meningiomas, their operation can be postponed slightly when the patients are tolerable.

Postoperative analgesia and opioid use following hip arthroscopy with ultrasound-guided quadratus lumborum block: a randomized controlled double-blind trial.

OBJECTIVE: To investigate the postoperative analgesic effect of ultrasound-guided quadratus lumborum block (QLB) in patients undergoing arthroscopic hip surgery. METHODS: Patients who were scheduled to undergo elective arthroscopic hip surgery were randomly assigned to the QLB (Q) or control (C) group (n = 40 each). After general anesthesia induction, unilateral QLB was performed under ultrasound guidance in the Q group. The amount of opioid use via patient-controlled analgesia (PCA) and the resting and movement pain visual analog scale (VAS) scores when the patient left the postanesthesia care unit (PACU) and 4, 8, 12, and 24 hours after surgery were recorded. Postoperative complications were recorded for both groups. RESULTS: At 24 hours post-surgery, opioid consumption amounts via PCA (48.4 [48.1-48.6] mL) in the Q group were significantly lower compared with the C group (52.0 [51.0-53.8] mL). A significant reduction in opioid consumption was observed between the two groups at each time point. Resting and movement VAS scores at each time point were significantly lower in the Q compared with the C group. CONCLUSIONS: Hip arthroscopy patients who received QLB and general anesthesia in combination had less pain and a lower opioid requirement within 24 hours postoperatively.

The Clinical Significance of O6-Methylguanine-DNA Methyltransferase Promoter Methylation Status in Adult Patients With Glioblastoma: A Meta-analysis.

BACKGROUND AND OBJECTIVE: Promoter status of O6-methylguanine-DNA methyltransferase (MGMT) has been widely established as a clinically relevant factor in glioblastoma (GBM) patients. However, in addition to varied therapy schedule, the prognosis of GBM patients is also affected by variations of age, race, primary or recurrent tumor. This study comprehensively investigated the association between MGMT promoter status and prognosis in overall GBM patients and in different GBM subtype including new diagnosed patients, recurrent patients and elderly patients. METHODS: A comprehensive search was performed using PubMed, EMBASE, Cochrane databases to identify literatures (published from January 1, 2005 to April 1, 2017) that evaluated the associations between MGMT promoter methylation and prognosis of GBM patients. RESULTS: Totally, 66 studies including 7,886 patients met the inclusion criteria. Overall GBM patients with a methylated status of MGMT receiving temozolomide (TMZ)-containing treatment had better overall survival (OS) and progression-free survival (PFS) [OS: hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.41-0.52, p < 0.001, Bon = 0.017; PFS: HR = 0.48, 95% CI 0.40-0.57, p < 0.001, Bon = 0.014], but no significant advantage on OS or PFS in GBM patients with TMZ-free treatment was observed (OS: HR = 0.97, 95% CI 0.91-1.03, p = 0.08, Bon = 1; PFS: HR = 0.76, 95% CI 0.57-1.02, p = 0.068, Bon = 0.748). These different impacts of MGMT status on OS were similar in newly diagnosed GBM patients, elderly GBM patients and recurrent GBM. Among patients receiving TMZ-free treatment, survival benefit in Asian patients was not observed anymore after Bonferroni correction (Asian OS: HR = 0.78, 95% CI 0.64-0.95, p = 0.02, Bon = 0.24, I2 = 0%; PFS: HR = 0.69, 95% CI 0.50-0.94, p = 0.02, Bon = 0.24). No benefit was observed in Caucasian receiving TMZ-free therapy regardless of Bonferroni adjustment. CONCLUSION: The meta-analysis highlights the universal predictive value of MGMT methylation in newly diagnosed GBM patients, elderly GBM patients and recurrent GBM patients. For elderly methylated GBM patients, TMZ alone therapy might be a more suitable option than radiotherapy alone therapy. Future clinical trials should be designed in order to optimize therapeutics in different GBM subpopulation.

The use of endoscopic-assisted burr-hole craniostomy for septated chronic subdural haematoma: A retrospective cohort comparison study.

OBJECTIVE: To complete a retrospective comparison of endoscope-assisted burr-hole craniostomy (EBHC) and ordinary burr-hole craniostomy (OBHC) in the treatment of septated chronic subdural hematoma (SCSH). METHODS: A retrospective case note review comparing EBHC and OBHC of SCSH was therefore performed. Data of patients with a SCSH for EBHC or OBHC during the period from January 2011 to December 2016 were retrospectively collected and analysed. Of 73 patients, 42 underwent EBHC and 31 patients were treated by OBHC. The primary outcome measure was recurrence rate and secondary outcome measures were clinical outcome at first postoperative day, discharge and 6 months, the length of hospital stay for neurosurgery, the operative time, and the placement time of drainage tube. RESULT: The rate of recurrence was significantly lower in the EBHC (0/42 0%) than in the OBHC (8/31, 25.8%) group (p = .0030). The rate of morbidity was significantly lower in the EBHC (2/42, 4.8%) than in the OBHC (11/31, 35.5%) group (p = .0121). At 30 days, mortality did not differ between groups. Significantly more patients treated with EBHC were alive at 6 months than were those with OBHC. No patient died as a consequence of the operative procedure in the both groups. A discharge GCS of 15 was recorded in more participants with EBHC than in those with OBHC. Gross neurological deficit was significantly less frequent in those with EBHC than in those with OBHC at first postoperative day and discharge, but did not differ at 6 month follow-up. The mean placement time of drainage tube was significantly less in those with EBHC (27.2 h) than in those with OBHC (52.0 h, p = .0055). The mean length of hospital stay for neurosurgery was 4 days in the EBHC group, while it was 5 days in the OBHC group (p = .0015). The mean hematoma reduction rate was significantly higher in those with EBHC than in those with OBHC at first postoperative day (85.3% vs 72.5%, p = .0037) and discharge (90.3% vs 85.1%, p = .0127). CONCLUSION: Comparing two minimally invasive procedure protocols for treatment of SCSH, EBHC is a safe and effective surgical technique. It significantly surpasses the results obtained in OBHC in lowering recurrence rate, morbidity rate, placement time of drainage tube, and length of hospital stay for neurosurgery. We recommend EBHC technique to be widely used in the treatment of SCSH, even common chronic subdural hematoma (CSH), subacute and acute subdural hematomas, acute epidural hematomas and empyemas to avoid large craniotomies, particularly in elderly patients, so that patients can receive the best treatment on the basis of minimal trauma.

Diagnostic Value and Safety of Stereotactic Biopsy in Acquired Immune Deficiency Syndrome Patients with Intracranial Lesions: Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic value and safety of stereotactic biopsy in acquired immune deficiency syndrome (AIDS) patients with intracranial lesions via meta-analysis. METHODS: Relevant cohort studies were identified through a literature search in PubMed, Embase, and Ovid from 1985 to October 1, 2016. Appropriate studies were identified per search criteria. Systematic review and meta-analysis were used to assess the diagnostic success rate, changed management rate, clinical improvement rate, mortality rate, morbidity rate, hemorrhage rate, hemorrhage in morbidity rate, and final histologic diagnosis results. Study-specific outcomes were combined per a random effects model. Outcomes were compared between the pre-highly active antiretroviral therapy (HAART) and post-HAART groups. Correlations between outcomes were assessed via meta-regression analysis. RESULTS: A total of 19 cohort studies with 820 patients were included in this meta-analysis. The weighted proportions per the random effects model were 92.2% (95% confidence interval [CI; 89.3%-94.5%]) for diagnostic success rate, 5.1% (95% CI [2.5%-8.3%]) for morbidity, and 0.7% (95% CI [0%-1.9%]) for mortality. The most common procedure-related morbidity was hemorrhage at 3.3% (95% CI [1.1%-6.3%]). Hemorrhage in morbidity was 78.0% (95% CI [51.4%-97.4%]). Management changed and clinical improvement were 60.4% (95% CI [49.4%-71.0%]) and 34.0% (95% CI [22.2%-46.8%]), respectively. The 4 most common diagnoses were primary central nervous system lymphoma (27.8%; 95% CI [20.2%-36.1%]), progressive multifocal leukoencephalopathy (PML) (21.0%; 95% CI [14.3%-28.4%]), toxoplasma encephalitis (TE) (20.3%; 95% CI [14.3%-27.0%]), and human immunodeficiency virus (HIV) encephalitis (4.1%; 95% CI [1.4%-7.6%]). Multiple diagnoses rate was 1.2% (95% CI [0.0%-3.6%]). HIV encephalitis rate was significantly higher in the post-HAART group than the pre-HAART group (17.9% vs. 3.2%, respectively; P = 0.0024). CONCLUSIONS: Stereotactic biopsy is a safe and effective way of diagnosing intracranial lesions in patients with AIDS. It is helpful for the differential diagnosis and for choosing a suitable therapy. The 4 most common intracranial lesions in patients with AIDS are lymphoma, PML, TE, and HIV encephalitis.

Activation of G-protein coupled estrogen receptor 1 improves early-onset cognitive impairment via PI3K/Akt pathway in rats with traumatic brain injury.

Previous studies experimentally reveal that G-protein coupled estrogen receptor 1(GPER) has neuroprotection against ischemic injury. However, its effect on traumatic brain injury (TBI) is less well-established. Cognitive impairment following human TBI is a common clinical observation, and TBI is considered as a risk factor for Alzheimer's disease (AD). This study aimed to observe the possible protective effect of GPER on early-onset cognitive impairment after a single TBI and investigate the cellular mechanism underlying its actions. We found that selective GPER agonist G-1 significantly reduced hippocampal CA1 neuronal loss and improved cognitive impairment in TBI rats. Although previous studies have shown that AD-like tau pathology occurs many years after both repetitive and single TBI, accumulation of hyperphosphorylated tau was not observed within days (detected at 24 h and 7d) after TBI. Furthermore, tau phosphorylation was not altered by G-1 treatment. It was found that G-1 administration caused an increase in p-Akt level. However, the neuroprotective effects of G-1 on spatial cognition and neuronal death were attenuated by PI3K/Akt inhibitor LY294002. These findings indicate that GPER agonist G-1 had protection on cognitive function via activation of PI3K/Akt signaling. Early-onset cognitive impairment following a single TBI was closely associated with acute hippocampal neuronal loss rather than tau pathology. This study suggests that early activation of GPER might be a promising therapeutic strategy for improvement of TBI-induced cognitive outcomes.

The effects of platelet apheresis on blood saving and coagulation in bilateral total hip replacement: A prospective study on 60 patients.

BACKGROUND: Preoperative platelet rich plasma (PRP) harvest has been used in cardiopulmonary surgery for more than 10 years. There is no previous study dealing with PRP in bilateral total hip replacement. This study was to investigate the effects of PRP on blood saving and blood coagulation function in patients with bilateral total hip replacement. PATIENTS AND METHODS: A prospective, randomized, clinical trial was conducted. Sixty patients were enrolled, including 30 patients undergoing PRP in the PRP group and 30 controls. The surgery time, total transfusion volume, blood loss, allogenic blood transfusion, autologous blood transfusion, urine volume, drainage volume, some blood parameters (including Fibrinogen, D-dimer, Prothrombin time, international normalizedratio, activated partial thromboplastin time, Platelet, Haemoglobin B), thrombelastogram (TEG) and blood-gas parameters were studied in the perioperative stage. The measurement data were analyzed statistically. RESULTS: There was no statistical difference between the two groups in baseline characteristics, surgery time, total transfusion volume, blood loss, autologous blood transfusion, etc. Allogenic blood transfusion in the PRP group was less than the control group with statistical difference (p = 0.024). Fibrinogen in the PRP group was higher than the control group (p = 0.008). Among the TEG indicators, activated clotting time and coagulation time K in the PRP group were less than the control group. Clotting rate and maximum amplitude in the PRP group were higher. The blood-gas parameters presented no statistical difference. CONCLUSION: The results suggested that PRP probably played a positive role in blood coagulation function as well as blood saving in patients with bilateral total hip replacement.

The efficacy of simultaneous bilateral axillary brachial plexus block under the guidance of neurostimulator or ultrasound: a prospective study.

PURPOSE: This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. METHODS: One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n = 60) or ultrasound (group U, n = 60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. RESULTS: The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p < 0.001). The procedure-related pain of group N was more serious than that of group U (p < 0.05). The patient satisfaction rate of group U was higher than that of group N (p < 0.05). The total plasma concentrations of ropivacaine in group N were comparable to those of group U, except for the value at 50 min after injection (p < 0.05). The free plasma concentrations of ropivacaine of group N at 5 min were significantly higher than that of group U (p < 0.001). No apparent serious adverse events were observed perioperatively in both groups. CONCLUSIONS: Simultaneous bilateral axillary brachial plexus block guided by neurostimulator or ultrasound in bilateral distal upper extremity surgery seems to have a low risk of local anesthetic toxicity and to be effective. The ultrasound-guided block is superior in terms of providing the same degree of anesthesia with shorter duration, less pain, and faster onset of sensory and motor blockades, which is important in clinical practice.

Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia.

BACKGROUND: Melatonin, a well-known antioxidant, has been shown to possess anti-invasive properties for glioma. However, little is known about the effect of melatonin on glioma cell migration and invasion under hypoxia, which is a crucial microenvironment for tumor progress. In addition, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are closely associated with cell migration and invasion. Therefore, we investigated the possible role of these kinases and its related signaling in the regulation of human U251 glioma cells behavior by melatonin under hypoxia. METHODS: The abilities of migration and invasion of U251 glioma cells were determined by wound healing and transwell assay in vitro. The intracellular production of reactive oxygen species (ROS) was measured by using the fluorescent probe 6-carboxy-2', 7'-dichorodihydrofluorescein diacetate (DCFH-DA). Immunofluorescence experiments and western blotting analysis were used to detect the expression level of protein. Small interfering RNAs (siRNA) was used to silence specific gene expression. RESULTS: The pharmacologic concentration (1 mM) of melatonin significantly inhibited the migration and invasion of human U251 glioma cells under hypoxia. The inhibitory effect of melatonin was accompanied with the reduced phosphorylation of FAK and Pyk2, and decreased expression of alpha v beta 3 (αvß3) integrin. Additionally, inhibition of αvß3 integrin by siRNA reduced the phosphorylation of FAK/Pyk2 and demonstrated the similar anti-tumor effects as melatonin, suggesting the involvement of αvß3 integrin- FAK/Pyk2 pathway in the anti-migratory and anti-invasive effect of melatonin. It was also found that melatonin treatment decreased the ROS levels in U251 glioma cells cultured under hypoxia. ROS inhibitor apocynin not only inhibited αvß3 integrin expression and the phosphorylation levels of FAK and Pyk2, but also suppressed the migratory and invasive capacity of U251 glioma cells under hypoxia. CONCLUSIONS: These results suggest that melatonin exerts anti-migratory and anti-invasive effects on glioma cells in response to hypoxia via ROS-αvß3 integrin-FAK/Pyk2 signaling pathways. This provides evidence that melatonin may be a potential therapeutic molecule targeting the hypoxic microenvironment of glioma.