Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma.

Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM's recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM.

Quantitative Anatomic Analysis and Clinical Application of Lumbar Spinous Process Split Laminotomy.

AIM: To investigate the feasibility and safety of lumbar spinous process split laminotomy by quantitative anatomic analysis. MATERIAL AND METHODS: Nine fresh adult human cadaveric specimens (including 45 lumbar segments) were divided into 3 groups randomly. The simulated operations and anatomic measurements were performed to evaluate the visibility angle and surgical corridor at different retraction widths (8 mm, 10 mm, and 12 mm). By measuring the width causing bony fracture in 45 lumbar segments, the safety margin of retraction width was determined. The findings of lumbar spinous process split laminotomy in one typical case were presented. RESULTS: At 8 mm retraction width, there was not enough surgical corridor for the operation procedures. At 10 mm and 12 mm retraction width, all operation procedures could be conducted smoothly. The 12 mm group presented a larger surgical corridor and shorter operative time compared with the 10 mm group. The imaging examination confirmed no bony fracture and articular capsule impairment. The visibility angle and exposure extent increased in proportion to the retraction width. The retraction width that resulted in the bony fracture ranged from 12.34 mm to 16.82 mm, with an average of (14.56 ± 1.73) mm. The positions of fracture were in the pedicle of the vertebral arch (68.9%), the lamina (26.7%), and the vertebral body (4.4%). CONCLUSION: The retraction width of 10 mm-12 mm is safe and effective. The micromanipulations such as tumor resection, nervous exploration, dural suture, etc. can be conducted smoothly via the surgical corridor. In addition, the retraction width of 12.34~16.82 mm could serve as a safety margin for surgical planning. Our findings may provide a quantitative reference for clinical application of lumbar spinous process split laminotomy.

The Influence of the Novel Computer-Aided Triage System Based on Artificial Intelligence on Endovascular Therapy in Patients with Large Vascular Occlusions: A Meta-Analysis.

OBJECTIVE: The integration of artificial intelligence (AI) with modern healthcare has become increasingly prominent. The purpose of this study is to explore the impact of the novel computer-aided triage system based on artificial intelligence (AI-CTS) on endovascular therapy (EVT) in patients with large vascular occlusions (LVO). This study marks the first comprehensive systematic review and meta-analysis on the subject. METHODS: A comprehensive study was performed on PubMed, Medline, Embase, Cochrane Library, and Chinese databases from their establishment to September 2023, in accordance with PRISMA recommendations. RevMan 5.4 software was used for summative analysis. The outcomes included door-to-groin (DTG) time, time from CT scan initiation to EVT, time from CT scan to reperfusion, and 90-day modified Rankin Scale (mRS). RESULTS: A total of 7 studies involving 752 participants were included in the meta-analysis. The pooled results demonstrated that patients in the post-AI group had less time of DTG [SMD, 0.54; 95% CI, 0.40-0.69; P < 0.00001] and CT scan to EVT [SMD, 0.57; 95% CI, 0.42-0.73; P < 0.00001], as well as less time of CTA to recanalization [SMD, 0.63; 95% CI, 0.36-0.90; P < 0.00001]. There was no significant difference between the 2 groups in terms of the mRS at 90 days [OR, 0.66; 95% CI, 0.43-1.01; P = 0.06]. CONCLUSIONS: The combination of AI-CTS and EVT has improved the therapy process for LVO patients. However, the improvement in mRS at 90 days was not significant; further research is warranted.

Anatomical Study of Cross-Transfer of the Contralateral C7 Nerve Through the Posterior Epidural Pathway of the Cervical Spine for the Treatment of Spastic Paralysis of the Upper Limbs.

BACKGROUND: This study explored the safety and feasibility of surgical treatment of spastic paralysis of the central upper extremity by contralateral cervical 7 nerve transfer via the posterior epidural pathway of the cervical spine. METHODS: Five fresh head and neck anatomical specimens were employed to simulate contralateral cervical 7 nerve transfer through the posterior epidural pathway of the cervical spine. The relevant anatomical landmarks and surrounding anatomical relationships were observed under a microscope, and the relevant anatomical data were measured and analysed. RESULTS: The posterior cervical incision revealed the cervical 6 and 7 laminae, and lateral exploration revealed the cervical 7 nerve. The length of the cervical 7 nerve outside the intervertebral foramen was measured to be 6.4 ± 0.5 cm. The cervical 6 and cervical 7 laminae were opened with a milling cutter. The cervical 7 nerve was extracted from the inner mouth of the intervertebral foramen, and its length was 7.8 ± 0.3 cm. The shortest distance of the cervical 7 nerve transfer via the posterior epidural pathway of the cervical spine was 3.3 ± 0.3 cm. CONCLUSIONS: Cross-transfer surgery of the contralateral cervical 7 nerve via the posterior epidural pathway of the cervical spine can effectively avoid the risk of nerve and blood vessel damage in anterior cervical nerve 7 transfer surgery; the nerve transfer distance is short, and nerve transplantation is not required. This approach may become a safe and effective procedure for the treatment of central upper limb spastic paralysis.

Multiple inflammatory pseudotumor formation after craniopharyngioma resection via an extended nasal endoscopic approach: A case report.

BACKGROUND: This report describes a case of intracranial multiple inflammatory pseudotumors (IP) after endoscopic resection of a craniopharyngioma, which is relatively rarely reported in the literature, and neurosurgeons should be aware of its existence. CASE SUMMARY: Herein, we report the case of a 56-year-old man who developed decreased visual acuity and blurred vision without obvious cause or inducement on April 27, 2020. To seek further treatment, he went to the Department of Neurosurgery, Clinical Medical College, Yangzhou University. After falling ill, there was no nausea, vomiting, limb convulsions, obvious disturbance of consciousness, speech disorders, cough, or persistent fever. The neurological examination findings were normal, and pituitary magnetic resonance imaging (MRI) revealed multiple nodules with abnormal signals in the sellar region. The diagnosis was craniopharyngioma. We performed total resection of the tumor via transnasal endoscopy, and the postoperative pathology suggested that the type of tumor was craniopharyngioma. Six months after the operation, the patient experienced sudden hearing loss in the right ear, tinnitus in both ears, and numbness on the right side of the face and head. Meanwhile, cranial MRI showed multiple IP. After steroid hormone and anti-inflammatory therapy, the above symptoms did not significantly improve. Finally, the patient's symptoms were well improved by surgery, and the postoperative pathological diagnosis was multiple IP. CONCLUSION: Intracranial inflammatory pseudotumor is a benign disease with slow progression, but the clinical symptoms and imaging findings are not typical, there are no pathological findings, and the diagnosis is relatively difficult. Most of the cases are treated by surgical resection, and the prognosis is good after surgery.

The effect of general anesthesia and conscious sedation in endovascular thrombectomy for acute ischemic stroke: an updated meta-analysis of randomized controlled trials and trial sequential analysis.

Objectives: General anesthesia (GA) and conscious sedation (CS) are common methods for endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). However, the risks and benefits of each strategy are unclear. This study aimed to summarize the latest RCTs and compare the postoperative effects of the two methods on EVT patients. Materials and methods: We systematically searched the database for GA and CS in AIS patients during EVT. The retrieval time was from the creation of the database until March 2023. The quality of the studies was evaluated using the Cochrane risk of bias tool. Random-effects or fixed-effects meta-analyses were used to assess all outcomes. Results: We preliminarily identified 304 studies, of which 8 were included. Based on the pooled estimates, there were no significant differences between the GA group and the CS group in terms of good functional outcomes (mRS0-2) and mortality rate at 3 months (RR = 1.09, 95% CI: 0.95-1.24, p = 0.23) (RR = 0.95, 95% CI: 0.75-1.22, p = 0.70) as well as in NHISS at 24 h after treatment (SMD = -0.01, 95% CI: -0.13 to 0.11, p = 0.89). However, the GA group had better outcomes in terms of achieving successful recanalization of the blood vessel (RR = 1.13, 95% CI: 1.07-1.19, p < 0.0001). The RR value for the risk of hypotension was 1.87 (95% CI: 1.42-2.47, p < 0.00001); for pneumonia, RR was 1.43 (95% CI: 1.07-1.90, p = 0.01); and for symptomatic intracerebral hemorrhage, RR was 0.94 (95% CI: 0.74-1.26, p = 0.68). The pooled RR value for complications after intervention was 1.03 (95% CI, 0.87-1.22, p = 0.76). Conclusion: In patients undergoing EVT for AIS, GA, and CS are associated with similar rates of functional independence. Further trials of a larger scale are needed to confirm these findings.

Anatomical Study and Clinical Application of Neuroendoscopic Transfarlateral Supracerebellar Infratentorial Approach.

BACKGROUND: Tumors in the petroclival region have challenged neurosurgeons. However, neuroendoscopy has been increasingly applied internationally. This study simulated a pure neuroendoscopic transfarlateral supracerebellar infratentorial approach for petroclival tumor resection from the cadaveric head and discussed the advantages and safety of this approach. METHODS: The anatomical structure for petroclival tumor resection was visualized using a pure neuroendoscopic transfarlateral supracerebellar infratentorial approach in 5 cadaveric heads. Ten cases with petroclival tumors were retrospectively analyzed and summarized between January 2020 and June 2021. All the cases had undergone surgery using a pure neuroendoscopic supracerebellar infratentorial approach. RESULTS: The anatomical structure of the petroclival region was exposed using the pure neuroendoscopic supracerebellar infratentorial approach, and the partial anatomical structure of the middle skull base was further exposed by incision of the tentorium in the cadaveric head. Among the 10 cases, the tumors of 6 cases were totally removed, and those of 4 cases were subtotally removed; no cases of intracranial infection or death occurred after surgery. CONCLUSION: The neuroendoscopic transfarlateral supracerebellar infratentorial keyhole approach is a safe and effective surgical method to treat petroclival lesions and invasive middle cranial fossa lesions.

Contralateral seventh cervical nerve transfer for central spastic arm paralysis: a systematic review and meta-analysis.

Objectives: The specific benefits of a contralateral cervical 7 nerve transplant in people with spastic paralysis of the upper extremity caused by cerebral nerve injury are unclear. To evaluate the efficacy and safety of contralateral C7 nerve transfer for central spastic paralysis of the upper extremity, we conducted a comprehensive literature search and meta-analysis. Materials and methods: PRISMA guidelines were used to search the databases for papers comparing the efficacy of contralateral cervical 7 nerve transfer vs. rehabilitation treatment from January 2010 to August 2022. The finishing indications were expressed using SMD ± mean. A meta-analysis was used to assess the recovery of motor function in the paralyzed upper extremity. Results: The meta-analysis included three publications. One of the publications offers information about RCTs and non-RCTs. A total of 384 paralyzed patients were included, including 192 who underwent CC7 transfer and 192 who received rehabilitation. Results from all patients were combined and revealed that patients who had CC7 transfer may have regained greater motor function in the Fugl-Meyer score (SMD 3.52, 95% CI = 3.19-3.84, p < 0.00001) and had superior improvement in range of motion compared to the rehabilitation group (SMD 2.88, 95% CI = 2.47-3.29, p < 0.00001). In addition, the spasticity in the paralyzed upper extremity significantly improved in patients with CC7 transfer (SMD -1.42, 95% CI = -1.60 to -1.25, p < 0.00001). Conclusion: Our findings suggested that a contralateral C7 nerve transfer, which has no additional adverse effects on the healthy upper limb, is a preferable method to restore motor function.

Endoscopic Anatomical Study of the Glabellar Keyhole Approach.

AIM: To observe the exposure range of a neuroendoscope through the glabellar approach and measure the anatomical parameters to provide a basis for clinical application. MATERIAL AND METHODS: A total of 10 adult cadaveric heads fixed with formalin were dissected by stratified local anatomy and simulated operation. The length of each point was measured from the corresponding anatomical mark of the anterior fossa on the bone window plate and analysed to clarify relevant surgical indications and feasibility to provide an anatomical basis for clinical application. RESULTS: The distance from the lower boundary of the bone window to the left anterior clinoid process was (61.97 ± 3.51) mm, the distance to the right anterior clinoid process was (62.21 ± 3.20) mm, the distance to the leading edge of the optic chiasma was (67.40 ± 5.38) mm, the distance to the sellar tubercle was (57.91 ± 2.64) mm, the distance to the centre of the saddle septum was (68.45 ± 4.88) mm; the distance to the midpoint of the endplate was (67.86 ± 4.91) mm, the distance to the anterior communicating artery was (60.89 ± 6.17) mm, the distance to the left posterior clinoid process was (67.56 ± 3.84) mm, the distance to the right posterior clinoid process was (66.78 ± 3.23) mm, the distance to the bifurcation of the left internal carotid artery was (69.45 ± 2.34) mm and the distance to the bifurcation of the right internal carotid artery was (68.01 ± 3.53) mm. CONCLUSION: The neuroendoscopic glabellar approach can effectively expose the anatomical structures of the midline anterior skull base and both sides near the sellar area and can be used to look for lesions in the midline anterior skull base.

Clinical study of puncture technique in single division of the trigeminal ganglion intumescentia.

OBJECTIVE: We explored the feasibility of single-division puncture in the ophthalmic division, maxillary division, and mandibular division of the trigeminal ganglion intumescentia (TGI) and the feasibility of radiofrequency treatment of trigeminal neuralgia. METHODS: According to the previous anatomical image studies, 3D Slicer software was used to analyze the CT images of the patients. The trigeminal ganglion fossa (TGF) was used as the imaging sign. TGI was identified in the sagittal plane along the fiber. The puncture path starts from the TGI center-foramen ovale line, extending outward to the epidermis as the needle insertion point, and extending inward to the division boundary. For lateral puncture, which is blocked by the mandible, the positions of closed mouth, open mouth, and over-open mouth were used. Multiple targets were generated using straight electrodes and curved electrodes to achieve full coverage of TGI. According to the preoperative design, general anesthesia surgery was performed. Xper CT was used for imaging, and the puncture was guided by Xper Guide. Radiofrequency treatment of TGI was conducted. RESULTS: In total, 45 patients with trigeminal neuralgia underwent 50 single-division TGI punctures. The procedure was smooth and the compliance with the design was good. Continuous radiofrequency (CRF) was performed, the VAS scores were 25 times at 70°C, 19 times at 65°C, two times at 60°C, and two times at 50°C (both in the ophthalmic division). Pulsed radiofrequency (PRF) was conducted two times. Within 24 h after the procedure, the VAS scores were all 0. From 1 to 7 days after the procedure, pain recurrence was found in three cases, of whom two cases received pulsed radiofrequency treatment. Patients were followed up for 1-24 months and there were no recurrence. After continuous radiofrequency at 65-70°C, the moderate tactile loss was observed, and nearly half of the patients had food residues on the surgical side after 6 months. After continuous radiofrequency at 60°C, there was mild tactile loss and no food residue. The tactile sensation was slightly decreased after continuous radiofrequency at 50°C, and the tactile sensation was normal the next day. CONCLUSION: Trigeminal ganglion intumescentia single-division radiofrequency is effective and feasible for the treatment of trigeminal neuralgia.

Anatomical Study and Clinical Application of Optic Canal Decompression Via Transethmoid-sphenoid Approach Under Endoscope.

This study aimed to evaluate the safety and accuracy of the endoscopic transethmoid-sphenoid approach for optic canal decompression. Twelve sides of 6 adult cadaveric heads fixed in formalin were selected to simulate optic canal decompression using the endoscopic transethmoid-sphenoid approach. Furthermore, this approach was used for optic canal decompression in 10 patients (11 eyes) with optic nerve canal injury. Related anatomical structures were observed using a 0-degree endoscope, and the anatomical characteristics as well as the surgical data were collected. The maximum effective widths of the cranial opening, orbital opening, and middle segment of the canal that could be drilled open endoscopically were 7.82±2.63, 8.05±2.77, and 6.92±2.01 mm, respectively. The angle between the line linking the center point of the tubercular recess with the midpoint of the cranial opening of the optic canal and the horizontal coordinate was 17.23±1.34 degrees. At the orbital opening of the optic canal, the ophthalmic artery was located directly inferior to the optic nerve in 2 cases (16.7%) and laterally inferior to the optic nerve in 10 cases (83.3%). Six of the operational eyes were effective while the remaining 5 were ineffective. No postoperative complications such as bleeding, infection, or cerebrospinal fluid leakage were observed during the follow-up period (6-12 mo). In conclusion, optic canal decompression positively impacts the prognosis of partial traumatic optic neuropathy. Furthermore, the endoscopic transethmoid-sphenoid approach for optic canal decompression is a minimally invasive procedure that provides direct access and adequate decompression. This technique is easy to master and suitable for clinical applications.

Endovascular treatment achieves better outcomes than best medical management in patients with M2 occlusion and high stroke severity: a meta-analysis.

BACKGROUND: The lack of randomized evidence makes it difficult to establish reliable treatment recommendations for patients with M2 occlusion. This study aims to compare the efficacy and safety of endovascular treatment (EVT) with best medical management (BMM) in patients with M2 occlusion, and to investigate whether the optimal treatment varies according to stroke severity. METHODS: Comprehensive literature retrieval was conducted to identify studies that directly compared the outcomes of EVT and BMM. According to stroke severity, the study population were classified into those with moderate-severe stroke and those with mild stroke. National Institute of Health Stroke Scale (NIHSS) scores ≥ 6 was defined as moderate-severe stroke, and NIHSS scores 0-5 as mild stroke. Random-effects meta-analyses were performed to measure the symptomatic intracranial hemorrhage (sICH) within 72 h, and the modified Rankin Scale (mRS) scores 0-2 and the mortality at 90 days. RESULTS: Totally, 20 studies were identified, including 4358 patients. In the moderate-severe stroke population, the EVT had 82% higher odds for mRS scores 0-2 (OR 1.82, 95% CI 1.34-2.49) and a 43% lower odds for mortality (OR 0.57, 95% CI 0.39-0.82) compared with the BMM. However, no difference was found in the sICH rate (OR 0.88, 95% CI 0.44-1.77). In the mild stroke population, no differences were observed in the mRS scores 0-2 (OR 0.81, 95% CI 0.59-1.10) or mortality (OR 1.23, 95% CI 0.72-2.10) between EVT and BMM, whereas EVT was associated with higher sICH rate (OR 4.21, 95% CI 1.86-9.49). CONCLUSION: EVT may be only beneficial for patients with M2 occlusion and high stroke severity, but not for those with NIHSS scores 0-5.

Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy.

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM). Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice. Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p < 0.05). Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.

PA2G4P4 Promotes Glioma Cell Migration and Tumorigenesis through the PTEN/AKT/mTOR Signaling Pathway.

Dysregulation of pseudogene expression is closely related to the progression of various cancers, including glioma. Proliferation-associated 2G4 pseudogene 4 (PA2G4P4) could affect cell viability and apoptosis of glioma cells. However, the specific regulatory mechanism of PA2G4P4 is not clear. In this paper, we found that PA2G4P4 overexpres-sion promoted glioma cell proliferation, migration and cell cycle progression, whereas PA2G4P4 knockdown inhibited cancer progression. Knockdown of PA2G4P4 also suppressed the tumorigenesis of glioma cells in vivo. Furthermore, knockdown of PA2G4 after overexpression of PA2G4P4 decreased the cell viability and migration ability to normal level. The protein level of a tumor suppressor gene phosphatase and tensing homolog (PTEN) was greatly decreased in U87 cells after PA2G4P4 overexpression, while increased after PA2G4 knockdown; on the contrary, the protein levels of P-AKT and P-S6 were obviously induced in U87 cells after PA2G4P4 overexpression, and decreased after PA2G4 knockdown. The cell ability, colony formation ability and cell migration ability were all recovered to normal level by adding an AKT inhibitor MK2206 to the glioma cells, which were induced by PA2G4P4 overexpression. Our results revealed that PA2G4P4 could regulate glioma cell proliferation and migration through PTEN/AKT/mTOR signaling pathway by targeting PA2G4 gene. PA2G4P4 may become a target for glioma treatment.

Neurod1 mediates the reprogramming of NG2 glial into neurons in vitro.

Neuronal defect and loss are the main pathological processes of many central nervous system diseases. Cellular reprogramming is a promising method to supplement lost neurons. However, study on cellular reprogramming is still limited and its mechanism remains unclear. Herein, the effect of Neurod1 expression on differentiation of NG2 glia into neurons was investigated. In this study, we successfully isolated NG2 glial cells from mice prior to identification with immunofluorescence. Afterwards, AAV-Neurod1 virus was used to construct Neurod1 overexpression vectors in NG2 glia. Later, we detected neuronal markers expression with immunofluorescence and real time quantitative polymerase-chain reaction (qRT-PCR). Besides, expression of MAPK-signaling-pathway-related proteins were detected by western blotting technique. Through immunofluorescence and qRT-PCR techniques, we observed that Neurod1 overexpression contributed to NG2 cells differentiated into neurons. Further experiments also showed that Neurod1 overexpression induced the activation of MAPK pathway, but PD98059 (a selective inhibitor of MAPK pathway) partly inhibited the neuronal differentiation induced by Neurod1 overexpression. These findings suggest that Neurod1 could promote NG2 glia cells differentiating into neurons, wherein the mechanism under the differentiation is related to activation of MAPK pathway.

The diagnostic and prognostic value of glial fibrillary acidic protein in traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVES: Over the years, blood biomarkers have been extensively applied for diagnostic and prognostic assessment of traumatic brain injury (TBI). Herein, we conducted a meta-analysis to evaluate the diagnostic and prognostic value of glial fibrillary acidic protein (GFAP) for TBI patients. METHODS: The online databases, including PubMed, Embase, Cochrane Library, CNKI, and WFSD, were systematically retrieved from inception until May 2021. The RevMan 5.3 software and Stata 15 were used to conduct data analysis. RESULTS: A total of 22 eligible studies comprising 3709 patients were included in this meta-analysis. The pooled results indicated that serum GFAP had a diagnostic value in detecting traumatic intracranial lesions (AUC 0.81; 95% CI 0.77-0.84; p < 0.00001). The pooled sensitivity and specificity were 0.93 (95% CI 0.81-0.98), and 0.66 (95% 0.53-0.77; p < 0.00001), respectively. For assessment of unfavorable outcome, the pooled sensitivity, specificity and AUC value were 0.66 (95% CI 0.54-0.76; p < 0.00001), 0.82(95% CI 0.72-0.90; p < 0.00001), and 0.82 (95% CI 0.76-0.88; p < 0.00001), respectively. Besides, GFAP exhibited a significant value in predicting mortality (AUC 0.81; 95% CI 0.77-0.84; p < 0.00001), with high sensitivity and specificity (0.86, 95% CI 0.79-0.92, p < 0.00001, and 0.66, 95% CI 0.52-0.77, p < 0.00001). The subgroup analysis indicated that the type of TBI and cut-off value were potential sources of heterogeneity, which influenced the pooled AUC values for mortality prediction. CONCLUSIONS: Our meta-analysis indicated that GFAP had diagnostic and prognostic value for TBI patients, especially during the early TBI.

Prognostic value of the systemic inflammation response index in patients with aneurismal subarachnoid hemorrhage and a Nomogram model construction.

OBJECTIVE: To investigate the prognostic value of inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived neutrophil/lymphocyte ratio (dNLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), prognostic nutritional index (PNI), and systemic inflammation response index (SIRI) in patients with aneurismal subarachnoid hemorrhage (aSAH), and then develop a Nomogram prognostic model. METHODS: We analysed 178 aSAH patients who underwent surgery at Subei People's Hospital of Jiangsu province from January 2015 to December 2017. Patients were divided into two groups according to Glasgow outcome scale (GOS) score at 3 months. Univariate and multivariate analysis were used to identify the association between inflammatory markers and prognosis. Subsequently, we identified the best cutoff of SIRI for unfavorable outcome using receiver operating characteristic (ROC) curve analysis and compared the clinical data between high and low SIRI levels. We further evaluated the additive value of SIRI by comparing prognostic nomogram models with and without it. RESULTS: A total of 47 (26.4%) patients had a poor outcome. Multivariate logistic regression analysis showed that SIRI was an independent risk factor of poor outcome. The SIRI of 4.105 × 109/L was identified as the optimal cutoff value, patients with high SIRI levels had worse clinical status and higher rates of unfavorable outcome. ROC analysis showed that a nomogram model combining the SIRI and other conventional factors showed more favorable predictive ability than the model without the SIRI. CONCLUSIONS: SIRI was independently correlated with unfavorable outcome in SAH patients, and the nomogram model combining the SIRI had more favorable discrimination ability.

Aberrant brain functional hubs convergence in the acute severe traumatic brain injury patients with rapidly recovering.

PURPOSE: We aimed to identify the aberrant functional hubs in patients with acute severe traumatic brain injury (sTBI) and investigate whether they could help inform prognosis. METHODS: Twenty-eight sTBI patients and health controls underwent imaging scanning. The graph-theoretical measure of degree centrality (DC) was applied to identify the abnormal brain functional hubs and conjoined with regions of interest-based analysis to investigate their interaction and impact on whole-brain. We further split sTBI patients into two subgroups according to their recovery to explore whether the fractional amplitude of low-frequency fluctuation (fALFF) roles in functional connectivity (FC) differential areas to help inform the patients' long-term prognosis. RESULTS: We identified the part of prefrontal cortex (PFC), precentral and postcentral gyrus (Pre-/Post-CG), cingulate gyrus (CgG), posterior medial cortex (PMC), and brainstem that could be core hubs whose DC was significantly increased in patients with acute sTBI. The interaction strength of the paired hubs could be enhanced (CG-PFC, CgG-PFC, CG-brainstem, CgG-brainstem, PMC-brainstem, and PFC-brainstem) and weakened (CG-CgG, CG-PMC, CgG-PMC, and PMC-PFC), compared with healthy controls. We also found abnormal FC in 5 hubs to whole-brain. The spontaneous brain activities in the FC differential regions [e.g., the fALFF and mean fALFF value] were valid to predict outcome at 6-month in patients with sTBI. CONCLUSION: We demonstrated a compensatory mechanism that part of brain regions will converge into abnormal functional hubs in patients with acute sTBI, which provides a potential approach to objectively predicting patients' long-term outcome.

Investigating the mechanism and prognosis of patients with disorders of consciousness on the basis of brain networks between the thalamus and whole-brain.

Purpose: This study aimed to investigate the changes in the functional connectivity between the bilateral thalamus and the whole-brain in patients with severe traumatic brain injury (sTBI) patients suffering from disorders of consciousness (DOC) and to explore their potential prognostic representation capacity. Methods: The sTBI patients suffering from DOC and healthy controls underwent functional magnetic resonance imaging. We defined patients with the Extended Glasgow Outcome Score (GOS-E) ≥ 3 as the wake group and GOS-E = 2 as the coma group. The differences in functional connectivity between sTBI and healthy controls and between wake and coma groups were compared. Based on the brain regions with altered functional connectivity between wake and coma groups, they were divided into 26 regions of interest. Based on the Z-values of regions of interest, the receiver operating characteristic analysis was conducted to classify the prognosis of patients. Results: A total of 28 patients and 15 healthy controls were finally included. Patients who had DOC indicated a significant disruption of functional connectivity between the bilateral thalamus and the whole-brain (FDR corrected, P < 0.0007). The functional connectivity strength (bilateral thalamus to whole-brain) was significantly different between coma patients who went on to wake and those who were eventually non-awake at 6 months after sTBI (Alphasim corrected, P < 0.05). Furthermore, the 26 regions of interest had a similar or even better prognostic distinction ability than the admission Glasgow coma score. Conclusion: The thalamus-based system of consciousness of sTBI patients suffering from DOC is disrupted. There are differences in the thalamus-to-whole-brain network between wake and coma groups and these differences have potential prognostic characterization capability.

si-PDGFRß-Loaded Exosomes Suppress the Progression of Glioma by Inhibiting the Oxidative Associated PI3K/Akt/EZH2 Signaling Pathway.

This study investigated the possibility of exosomes loaded with si-PDGFRß ability to suppress the progression of glioma. Common gliomas develop from neuroglial progenitor cells. Many variables affect the survival rate and occurrence of gliomas. Understanding oxidative stress processes and creating new, efficient treatments are crucial because oxidative stress is linked to the development of brain tumors. For this purpose, selected clinical samples were subjected to various tests like quantitative real-time PCR, Cignal Finder RTK signaling 7-pathway reporter array analysis, CCK-8 analysis, flow cytometry, and immunoblotting. Here, we demonstrated that PDGFRß expression was increased in glioma patients. Following that, cell-derived exosomes were extracted and collected and traced in vivo, and selected tissue samples were subjected to immunohistochemical analysis. The results indicated that the knockdown of PDGFRß (si-PDGFRß) inhibited the proliferation of glioma cells. Besides this, si-PDGFRß-loaded exosomes induced a similar antitumor effect in glioma cells. The anticancer effect of si-PDGFRß-loaded exosomes was mediated by the inactivation of the PI3K/Akt/EZH2 pathway. Finally, we verified that this exosome delivery system, si-PDGFRß-loaded exosomes, had robust targeting and no associated toxicity. In conclusion, the study confirmed that si-PDGFRß-loaded exosomes inhibit glioma progression via inactivating the PI3K/Akt/EZH2 signaling pathway.