BackgroundCranioplasty following decompressive craniectomy in patients requiring concurrent cerebral revascularization presents a surgical challenge. While traditional end-to-side bypass may compromise scalp perfusion, a combined single-stage procedure integrating extracranial-to-intracranial (EC-IC) bypass with cranioplasty offers a potential strategy for consolidating treatment, reducing cumulative procedural risks, and optimizing recovery.ObjectiveTo assess the feasibility of a single-stage procedure integrating superficial temporal artery (STA)-middle cerebral artery (MCA) side-to-side (S-S) anastomosis with cranioplasty and analyze the postoperative hemodynamic flow distribution.ResultsTwo patients successfully underwent single-stage STA-MCA S-S microvascular anastomosis with cranioplasty. Good patency of the STA-MCA S-S anastomosis was confirmed by both intraoperative indocyanine green videoangiography (ICG-VA) and postoperative digital subtraction angiography (DSA). On the postoperative DSA, a similar hemodynamic blood flow pattern was observed in both patients, and the proximal STA provided antegrade blood flow to the recipient MCA and the distal STA. No postoperative complications, including cerebral infarction, cerebral hyperperfusion syndrome, or wound healing issues, were observed.ConclusionsA single-stage combined S-S EC-IC anastomosis and cranioplasty procedure offers a viable, safe, and effective surgical strategy for patients requiring EC-IC revascularization and cranioplasty after craniectomy.

BACKGROUND Meningiomas arising from the dorsum sellae and upper clival region are extremely rare and pose significant surgical challenges due to their deep midline location and intimate relationships with critical neurovascular structures. Optimal surgical management remains controversial. OBSERVATIONS The authors present the case of a 66-year-old woman with progressive bilateral visual loss secondary to a large dorsum sellae meningioma. The tumor was resected through a single-stage mini-combined transpetrosal approach. This approach enabled early devascularization, clear visualization of neurovascular anatomy, and preservation of critical structures. The patient had a favorable postoperative course without complications. LESSONS The mini-combined transpetrosal approach provides a versatile and effective surgical corridor for tumors of this region. Careful preoperative planning and detailed knowledge of microsurgical anatomy are essential to maximize tumor removal and minimize morbidity. https://thejns.org/doi/10.3171/CASE25839

Background In rare cases, the superficial temporal artery (STA) is not the optimal donor vessel for extracranial-intracranial (EC-IC) bypass procedures. This situation can arise due to factors such as congenital abnormalities, hypoplastic development, trauma-related alterations, or prior surgical interventions. In such scenarios, a well-developed robust and sizable posterior auricular artery (PAA) can be considered a viable alternative for facilitating EC-IC revascularization surgeries. Objective To assess the feasibility of the surgical technique for posterior auricular artery (PAA) and middle cerebral artery (MCA) side-to-side (S-S) microvascular anastomosis, and to explore the blood flow distribution patterns following the establishment of PAA-MCA S-S anastomosis. Results A PAA-MCA S-S microvascular anastomosis was successfully performed. Intraoperatively, indocyanine green videoangiography (ICG-VA) confirmed immediate anastomotic patency, which was further validated by digital subtraction angiography (DSA). The recipient MCA received blood flow from two directions: antegrade blood flow originated from the proximal preanastomotic PAA, whereas retrograde blood flow traveled from the distal postanastomotic PAA via the ipsilateral and contralateral OAs. Conclusions Side-to-side microvascular anastomosis between the posterior auricular artery and middle cerebral artery is an effective alternative revascularization strategy in moyamoya disease. This approach optimizes the blood supply to the recipient MCA territory through dual-directional flow from the donor PAA, enhancing hemodynamic augmentation.

Objective:To evaluate a surgical strategy for hemorrhagic brainstem cavernous malformations by assessing 1) the impact of surgical timing (hemorrhage-to-surgery interval), and 2) the utility of preoperative diffusion tensor imaging (DTI) tractography for corticospinal tract (CST) preservation. Methods:In a retrospective cohort of 41 consecutive patients, the hemorrhage-to-surgery interval was stratified into acute (<3 weeks), subacute (3-8 weeks), and delayed (>8 weeks). Preoperative DTI tractography for CST mapping was utilized in 24 patients (DTI group) and not in 17 (non-DTI group); assignment was determined by magnetic resonance imaging scanner availability rather than clinical selection. The primary outcome was unfavorable functional status (modified Rankin scale score >2) at final follow-up. Results:The median hemorrhage-to-surgery interval was 53.0 days. Delayed surgery independently predicted unfavorable outcome at discharge (adjusted odds ratio, 9.03; 95% confidence interval, 1.10-73.94; p=0.04). Preoperative DTI was associated with a significantly lower rate of postoperative motor deterioration at discharge (12.5% vs. 47.1%; p=0.04). Subgroup analysis showed that the protective effect of DTI was significant only in the delayed surgery group (p=0.04), whereas among patients operated within 8 weeks, motor deterioration rates were low regardless of DTI use (16.7% vs. 16.7%; p=1.00). Persistent postoperative motor deficit was the strongest determinant of long-term disability (44.4% vs. 3.1%; p=0.006). Conclusion:A hemorrhage-to-surgery interval exceeding 8 weeks independently predicts poorer early functional recovery. Preoperative DTI tractography reduces postoperative motor deficits-the key driver of long-term disability-with its benefit most pronounced in the delayed surgery setting. We propose a risk-stratified, dual-emphasis strategy : timely intervention within 8 weeks when feasible, complemented by DTI tractography, which is particularly valuable in mitigating the increased risks of delayed surgery. This framework offers a practical, evidence-informed approach for optimizing functional outcomes.

Glioblastoma (GBM) represents one of the most challenging tumor types to treat clinically, characterized by an exceedingly poor patient prognosis. This is primarily attributable to the ambiguous molecular mechanisms that hinder the advancement of targeted therapies. Here, PRMT3 is identified as a key driver of tumorigenesis in GBM. Bioinformatics and clinical data reveal that high expression of PRMT3 in glioma cells is closely correlated with poor patient prognosis. Functional experiments demonstrate that PRMT3 overexpression enhances the proliferative capacity of GBM cells. Mechanistically, PRMT3 interacts with Y-box binding protein 1 (YBX1), and catalyzes the arginine methylation of YBX1 protein at R69 within its cold-shock domain. Subsequently, it was found that methylated YBX1 binds to 5-methylcytosine (m5C)-modified E2F1 mRNA and stabilizes its transcription, significantly promoting the expression of E2F1. The resulting PRMT3-YBX1-E2F1 axis sustains high E2F1 protein levels, activates a proliferation-associated transcriptional program, and is essential for GBM cell proliferation in vitro and in vivo . Meanwhile, the PRMT3 inhibitor SGC707 and the non-methylated YBX1 peptide significantly inhibited the proliferation of GBM cells. Our findings underscore that PRMT3 stabilizes E2F1 transcription through methylation of YBX1 at R69, promoting GBM tumorigenesis, and highlight the PRMT3-YBX1-E2F1 axis as a potential therapeutic target for GBM treatment.

Patients with recurrent high-grade glioblastoma have a median survival of 6-8 months, with limited therapeutic options. In recent years, interest has grown in applying chimeric antigen receptor T (CAR-T) cells to solid cancers, including advanced gliomas. Here we generated off-the-shelf CRISPR-Cas9–edited IL-13Rα2-specific allogeneic universal CAR-T cells (MT026) by disrupting the endogenous TCR to prevent graft-versus-host disease and knocking out HLA class I molecules to mitigate the host-versus-graft response, and observed minimal NK-cell–mediated rejection in preclinical studies. In a first-in-human, single-center, open-label investigator-initiated trial (ChiCTR2000028801) in patients with high-grade glioma with prior therapy failure and short life expectancy, intrathecal injection of MT026 via lumbar puncture (1.0-3.0×10^7 cells per dose) demonstrated favorable tolerability and safety (primary outcome), pharmacokinetic characteristics, and preliminary clinical activity (secondary outcomes). Among the five patients enrolled, one achieved a complete response and three achieved partial responses. No grade ≥3 adverse events were observed; the predominant treatment-related toxicities were grade 1-2 pyrexia, hypoxia, and vomiting. Trial enrolment was halted after enrolment of the first five patients, however these preliminary clinical data support the potential benefit of locally administered allogeneic universal CAR-T cell therapy for recurrent glioblastoma. Off-the-shelf, on-demand allogeneic CAR-T cells could represent a therapeutic alternative to autologous products for cancer therapy. Here the authors report the preclinical characterization of off-the-shelf CRISPR-Cas9– edited IL-13Rα2-specific allogeneic universal CAR-T cells and the results of a first-in-human phase I trial in patients with high-grade glioma.

2012 Background: Recurrent glioblastoma (GBM) has a median survival of less than 9 months. NeuroD1 is a neural transcriptional factor that can reprogram both glial cells and glioma cells into neuron-like cells, suppressing the proliferation of glioma cells and inducing cell death, extending the life span of animal models carrying glioblastoma. Therefore, scAAV6-NeuroD1 (NXL-004), a self-complementary adeno-associated virus 6 vector delivering NeuroD1, was developed to initiate a first-in-human study in patients with recurrent malignant glioma (ChiCTR2400080362). Methods: This is a single arm, open-label, dose-escalation study. The primary endpoint was safety, and the secondary endpoint was preliminary efficacy. Enrolled patients must have pathologically confirmed recurrent malignant glioma after standard therapy including surgery and chemoradiotherapy. NXL-004 was delivered intracavitary post-resection or intratumorally post-biopsy during surgery. Three dose levels (from 4.0x10 12 vg to 4.0x10 13 vg) were evaluated, using an accelerated dose escalation design. Up to two additional doses were allowed via an Ommaya reservoir at 2~4-week intervals after surgery. Results: 11 patients (median age 48.0, 81.8% male) were enrolled between 3/2024 and 6/2025. All patients had recurrent WHO grade 4 astrocytoma (10/11 IDH wild, 6/11 MGMT-unmethylated). Ten patients received repeat tumor resection plus intracavitary injection of NXL-004 (1 at low-dose, 3 at medium-dose, and 6 at high-dose), and one received biopsy plus intra-tumoral injection (low dose). All patients were included in the safety and efficacy analysis. No drug-related serious adverse event (SAE) or dose-limiting toxicities (DLT) was observed. All AEs related to NXL-004 were grade 1–2 (fever: 8/11; rash: 1/11; seizure: 1/11). Two grade 3 AEs (hemiplegia, meningitis) were reported but considered unrelated to the drug. Per RANO 2.0 criteria, the best overall response included 1 complete response (CR) and 5 stable disease (SD), yielding a disease control rate (DCR) of 54.5% (6/11). The median overall survival for all treated patients was 13.2 ± 2.0 months (95% CI: 9.3-17.1) from the first dose and 25.2 ± 1.2 months (95% CI: 23.0-27.5) from initial diagnosis. The first enrolled patient survived >18 months after dose. In the high-dose group, a higher DCR of 66.7% (4/6) was observed, with one patient achieving CR and one with SD surviving without progression >6 months (9 and 7 months, respectively, both ongoing). At a median follow-up of 9.0 months for this group, 5 patients were still alive, with 1 patient deceased (OS: 13.2 months). Conclusions: To our knowledge, this is the first clinical evidence of in vivo AAV-based trans-differentiation gene therapy for cancer treatment. NXL-004 showed favorable safety and encouraging efficacy, indicating that AAV-based cell reprogramming approach may represent a new modality for the treatment of glioma. Clinical trial information: ChiCTR2400080362.

Objective:Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease. The precise etiology and pathogenesis of PD remain unclear. Human wild-type α-synuclein has been implicated in PD pathogenesis. The objective of this study is to examine the role of α-synuclein in PD by establishing a rat model of substantia nigra degeneration and Motor behavioral changes through the induced overexpression of human α-synuclein. Methods:Rats were randomly assigned to either the Negative control group or the adeno-associated virus serotype 9 (AAV9) treatment group. Animals in the AAV9 group received 2.5 μL of AAV9 expressing human wild-type α-synuclein, while those in the Negative control group received an equal volume of AAV9 expressing green fluorescent protein via stereotactic unilateral injection into the substantia nigra pars compacta. Behavioral assessments were conducted at 1-, 3-, and 8-weeks following virus administration. Tyrosine hydroxylase and human α-synuclein expression in the substantia nigra pars compacta were analyzed. Additionally, dopamine, dihydroxyphenylacetic acid, and homovanillic acid levels in the striatum were quantified. Results:After 3 weeks of virus induction, neurodegeneration of the right substantia nigra was observed, with a reduction in the number of tyrosine hydroxylase-immunopositive neurons in the AAV9 group. By 8 weeks, substantia nigra neurodegeneration had further progressed, and animals in the AAV9 group exhibited apomorphine-induced asymmetrical rotation and altered forelimb use. Conclusion:Overexpression of human wild-type α-synuclein led to substantia nigra degeneration and Motor behavioral changes in rats, providing a viable model for exploring the pathogenesis of Parkinson's disease. Limitations include the 8-week observation window and the absence of neuroinflammation markers.

BACKGROUND: Side-to-side microvascular anastomosis is the most difficult type of anastomosis. The best way to master microvascular anastomosis technique is deliberate practice in the microsurgical laboratory. METHODS: Three types of side-to-side microvascular anastomosis using the rat abdominal vessels were presented. First, we present step-by-step technical details of common iliac artery (CIA)-CIA side-to-side microvascular anastomosis between 2 perfectly matched common iliac arteries via the in situ intraluminal suturing technique. Then, we present 2 arteriovenous side-to-side anastomosis training models using the same suturing technique: one with the CIA-common iliac vein (CIV) (CIA-CIV anastomosis) and the other with the abdominal aorta (AA) and inferior vena cava (IVC) (AA-IVC anastomosis). Diameters of CIA, CIV, AA, and IVC; the length of arteriotomy or venotomy; and the suturing time were recorded. The patency rates were evaluated immediately after the anastomosis was completed and 30 minutes later. RESULTS: In CIA-CIA side-to-side anastomosis, the bilateral CIAs were perfectly matched in terms of thickness, texture, and consistency. The vascular walls of the CIV and IVC were very thin, and they became transparent and collapsed after being cut open. A small-diameter thick walled artery was anastomosed to a large-diameter, very thin, and fragile vein in the CIA-CIV and AA-IVC arteriovenous anastomoses. Three types of side-to-side anastomosis using the rat abdominal vessels were successfully performed; 100% patency rates were achieved immediately and 30 minutes postoperatively. CONCLUSIONS: Three types of side-to-side microvascular anastomosis training models using abdominal vessels could be used to mimic different microvascular anastomotic situations.

The intra- and intertumoral heterogeneity of gliomas present major challenges to effective chemotherapy. This study explored the combined effects of PRMT5 and MAT2A inhibitors on glioma progression. The expression of drug targets was determined in cell models using western blotting and immunofluorescence assay. CCK-8, colony-formation, EdU fluorescence, and flow cytometry cell cycle assays were conducted to assess the effect of the drugs on cell proliferation. Additionally, TUNEL fluorescence assay, flow cytometry apoptosis assay, western blotting, and comet assay were used to evaluate drug-induced apoptosis and DNA damage. Immunohistochemistry was used to validate the effect of the drugs in a 3D glioma organoid model. Patient-derived orthotopic xenograft models were used for in vivo efficacy evaluations. Lastly, transcriptome sequencing was used to elucidate the mechanism of action of the drugs, which was confirmed using western blotting. In phenotypic experiments, PRMT5 inhibitors reduced SDMA levels, inhibited cell proliferation, and promoted apoptosis in glioma models. The combination of PRMT5 inhibitors with MAT2A inhibitors enhanced synthetic lethality, leading to more potent antitumor effects. In vivo studies demonstrated that the drug combination significantly inhibited tumor growth and prolonged survival time. Our study proved the combination of PRMT5 and MAT2A inhibitors may induce synthetic lethality by downregulating the PI3K-AKT pathway, indicating the potential of this approach in treating gliomas.

Superficial temporal artery (STA)-middle cerebral artery (MCA) side-to-side microvascular anastomosis can achieve the same clinical effects as traditional STA-MCA end-to-side anastomosis in extracranial-intracranial revascularization surgery, furthermore, STA-MCA side-to-side anastomosis has the lower risk of postoperative cerebral hyperperfusion syndrome (CHS) and the potential to recruit all scalp arteries as the donor sources via self-regulation. Therefore, STA-MCA side-to-side microvascular anastomosis seems to be a revascularization strategy superior to traditional STA-MCA end-to-side anastomosis. In this study, we presented seven cases in which a STA-MCA side-to-side microvascular anastomosis was performed with a 4–5 mm long arteriotomy using the in-situ intraluminal suturing technique. Superficial temporal artery (STA)-middle cerebral artery (MCA) side-to-side anastomosis was performed in seven patients using the in-situ intraluminal suturing technique. The diameters of the recipient MCA and the donor STA were approximately 0.94 mm (range 0.8–1.4 mm) and 1.65 mm (range 1.4–2.0 mm), respectively, and the length of the arteriotomy was approximately 4.71 mm (range 4–5 mm). The MCA was temporarily occluded in approximately 25.00 min (range 20–29 min). 100

Parkinson 's disease (PD) is a common neurodegenerative disease. Aggregates formed by α-synuclein (α-Syn) are the main pathological changes of PD. In this study, the effects of Calcium homeostasis modulator 2 (Calhm2) on α-syn-induced neurotoxicity in PD were evaluated. Primary neurons were treated with α-Syn PFF to mimic the PD cellular model. Genes and proteins were evaluated utilizing RT-qPCR, Western blot and immunofluorescence, respectively. Cell damage was assessed using CCK-8 and LDH assay. Cellular oxidative stress was assessed via the detection of SOD, GSH and ROS level. Mitochondrial membrane potential, ATP level, AIF nuclear translocation and intracellular Ca2+ were determined for the assessment of Parthanatos. HE and immunofluorescence of TH and NeuN was detected pathological changes in vivo. α-Syn PFF administration greatly resulted in oxidative stress, calcium overload and PARP-1 dependent Parthanatos in primary neurons. Following α-Syn PFF administration, Calhm2 and Calhm3, key calcium homeostasis modulator (Calhm) proteins, were markedly elevated in neurons, while Calhm1 expression exhibited a little change. In addition, suppression of Calhm2 obviously mitigated α-Syn PFF-induced oxidative stress injury, calcium overload and PARP-1 dependent Parthanatos in vitro. Similarly, in vivo results demonstrated that α-Syn PFF treatment led to PARP-1-dependent Parthanatos and nerve injury, while these effects were reversed by Calhm2 knockdown. Calhm2 repression lightened α-Syn aggregation-induced neurotoxicity and PARP-1-dependent Parthanatos in PD, providing a novel therapeutic target for PD treatment.

Protein arginine methyltransferase 1 (PRMT1), the predominant type I protein arginine methyltransferase, plays a crucial role in normal biological functions by catalyzing the methylation of arginine side chains, specifically monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), within proteins. Recent investigations have unveiled an association between dysregulated PRMT1 expression and the initiation and progression of tumors, significantly impacting patient prognosis, attributed to PRMT1’s involvement in regulating various facets of tumor cell biology, including DNA damage repair, transcriptional and translational regulation, as well as signal transduction. In this review, we present an overview of recent advancements in PRMT1 research across different tumor types, with a specific focus on its contributions to tumor cell proliferation, metastasis, invasion, and drug resistance. Additionally, we expound on the dynamic functions of PRMT1 during distinct stages of cancer progression, elucidating its unique regulatory mechanisms within the same signaling pathway and distinguishing between its promotive and inhibitory effects. Importantly, we sought to provide a comprehensive summary and analysis of recent research progress on PRMT1 in tumors, contributing to a deeper understanding of its role in tumorigenesis, development, and potential treatment strategies.

Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.

AIM:To present a technique for tightening continuous suture loops in microvascular side-to-side anastomosis with a microneedle.MATERIAL AND METHODS:The technique for tightening continuous suture loops with a microneedle was presented in side-to-side microvascular anastomosis in chicken thighs arteries and rat common carotid arteries. After all the spiral continuous suture loops were loosely placed, the tip of the microneedle was used to precisely and gently tighten the second suture loop, then microforceps was used to pick this loop up and gently tighten it, while the body of the microneedle was gently applied to create a counterforce on the inner or outer surface of the vessel to help tighten the first loop under appropriate tension and place it in an appropriate position.RESULTS:With this technique the author described, there is no need to change to any other surgical instruments during anastomosis, and these continuous suture loops in continuous microvascular anastomosis could be effectively tightened with a microneedle. And the technique was successfully applied in side-to-side microvascular anastomosis in chicken thighs arteries and rat common carotid arteries.CONCLUSION:Microneedle could be safely and effectively used as a microretractor to tighten the continuous suture loops in continuous microvascular anastomosis. The judicious and discreet use of a microneedle as a multifunctional instrument for functions other than suturing could minimize the exchange of instruments and improve operative efficiency.

Abstract BACKGROUND Optimal treatment for recurrent glioblastoma is yet to be definitely established. Development of new therapeutic approaches for recurrent glioblastoma are challenging due to multiple factors, including the immunosuppressive tumor microenvironment, the rapid disease progression, the difficulty for large molecules to cross blood brain barrier, the difficulty of collecting/testing tumor tissues. In the past, intra-ventricular infusion of IL-13Rα2-targeted autologous chimeric antigen receptor-T (CAR-T) cells has shown potent anti-tumor activity in one patient with recurrent glioblastoma. However, patients with malignant glioma often suffer from diminished anti-tumor lymphocyte response, with decreased cell count, exhausted function, or even incompetent in vitro expansion. Allogeneic chimeric antigen receptor (CAR) T cell therapy presents an alternative treatment paradigm and brings new hope for these patients. METHODS We initiated a prospective exploratory study in which MT026, an IL-13Rα2-specific allogeneic universal CAR-T cell preparations, was administered monthly via intra-lumbar injection in patients with IL-13Rα2-positive recurrent glioblastoma until disease progression, unacceptable toxicity, withdrawal of consent, death, loss to follow up, or discontinuation for patients’ benefit at investigator’s discretion. The primary end point was occurrence and severity of adverse events. Secondary end points included overall survival, 12-month survival rate, progression-free survival, objective response rate, duration of response, disease control rate and pharmacokinetic parameters. RESULTS A total of 5 patients, of whom 4 had Karnofsky Performance Scores (KPS) of <70 and only 1 was 90 and all had wild type IDH1/2 and unmethylated MGMT promoter, received MT026 followed by long-term follow-up till the patients’ death. Among the 5 patients, 1 patient (20%) had a complete response and overall survival of up to 17.5 months, 3 patients (60%) had partial responses, and 1 patient (20%) with stable disease, with an overall objective response rate of 80% and disease control rate of 100%. The mean OS was 10.4 months (95% confidence interval [CI], 4.5 to 16.2). The mean PFS was 5.6 months (95% CI, 3.1 to 8.2). The most common treatment-related abnormal laboratory test and symptom were increased cerebrospinal fluid (CSF) interleukin-6 (5/5, 100%) and fever (4/5, 80%), respectively. No adverse events of grade 3 or greater related to MT026 was reported. All the adverse events recovered or were relieved after treatment. No typical or severe cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome occurred. No graft-versus-host disease was observed. MT026 showed an expansion of approximately 1 day and persistence of over 30 days. CONCLUSIONS In patients with recurrent glioblastoma, MT026 resulted in a significantly longer overall survival and a higher objective response rate than history data. MT026 was not associated with any adverse events or toxic effects of grade 3 or higher. (Funded by Chongqing International Institute for Immunology; Chinese Clinical Trial Registry number, ChiCTR2000028801.)

Objective:To investigate the feasibility of establishing a side-to-side microvascular anastomosis training model by using the femoral artery and vein in rats.Methods:Twenty male SD rats were used in the study. After left-sided femoral arteries and veins were carefully dissected, side-to-side microvascular anastomosis was performed between femoral artery and vein via continuous suturing technique. The diameter of femora artery and vein, the length of the arteriotomy or venotomy, the distance between the corner of the arteriotomy and the temporary clip and suturing time were documented. Patency of those anastomoses was evaluated immediately, 30 min and 7 days after the procedure.Results:Twenty side-to-side microvascular anastomoses between femoral artery and vein were successfully performed in 20 rats, and the operation success rate was 100%. The diameter of femoral artery and vein was 0.68±0.11 mm (0.50-0.80 mm) and 1.21±0.18 mm (1.00-1.50 mm) respectively. The length of the arteriotomy or venotomy was 2.32±0.22 mm (2.00-2.60 mm). The distance between the corner of the arteriotomy and the temporary clip was 1.00-2.50 mm. The total suturing time was 29.2±3.0 min (26-34 min). The patency rate of 100% was achieved immediately, 30 min and 7 days after the procedure.Conclusion:Side-to-side microvascular anastomosis training model between rat femoral artery and vein is a feasible and effective side-to-side microvascular anastomosis training model.

Background : Instead of only practicing these perfectly matched end-to-side anastomoses in microsurgical laboratories, we must learn how to perform these so-called “imperfect” end-to-side anastomoses in the laboratory. Methods Three types of end-to-side microvascular anastomoses using the rat common iliac artery (CIA), one with the proximal end of the CIA to the contralateral side of the CIA, another with the distal end of the CIA to the contralateral side of the CIA, and the third with the distal end of the CIA to the ipsilateral side of the common iliac vein (CIV), were presented to simulate different end-to-side anastomosis situations in a microsurgical laboratory. Diameters of CIA and CIV, distances between temporary clips, the length of arteriotomy or venotomy, and the distribution of stitches were recorded. The patency rates were evaluated immediately after the anastomosis was completed and 30 min later. After animal euthanasia, the donor vessel was cut close to the anastomotic site, and the orifice size and intimal attachment were evaluated by inspecting them through inside the vessel. Results The diameters of the CIA and CIV were 0.8–1.2 mm and 1.2–1.5 mm, respectively. The end-to-side microvascular anastomosis arteriotomy or venotomy is approximately 2.00–2.50 mm, the distance between the aneurysm clips on the recipient CIA or CIV is approximately 4.00–7.00 mm, and the distance between the corner of the arteriotomy or venotomy and the temporary aneurysm clip was 1.00–3.00 mm. Three types of end-to-side anastomoses using the CIA were successfully performed, and 100% patency rates were achieved immediately and 30 min postoperatively. Good distribution of stitches, wide orifice, and intimal attachment were recorded in the study in all groups. Conclusions Three types of end-to-side anastomoses using rat CIAs could be efficiently used to mimic three different anastomotic situations.

目的 本研究旨在探究巴特朗菲教授所提倡的,亦是本科室在实践中常规应用的术中硬脑膜悬吊技术,探究其对术中硬脑膜修补的优势特点,以及对术后脑脊液漏等并发症的预防效果.方法 收集于我科行幕下手术的病例共 88 例,术中分别采用了巴氏悬吊技术和普通牵拉技术,采用回顾性分析方法,对这两种技术在术后脑脊液漏发生情况及其相关因素进行了对比统计分析.结果 采用巴氏悬吊技术的患者其发生脑脊液漏、皮下积液甚至颅内感染的概率明显低于采用传统牵拉技术的患者(P<0.05),此类术后并发症的发生率与硬脑膜修补材料的选择无明显相关性.结论 巴氏悬吊技术能有效保持硬脑膜张力,有利于关颅阶段硬脑膜的水密缝合,有效减少术后脑脊液漏等并发症的发生.

PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.