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1.
Carcinogenesis ; 45(7): 487-499, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38422369

RESUMO

Ferroptosis is a new form of regulated cell death caused by the iron-dependent peroxidation of phospholipids and is related to cell metabolism, redox homeostasis and various signalling pathways related to cancer. The long non-coding RNA (lncRNA) KB-1460A1.5 acts as a tumour suppressor gene to regulate tumour growth in gliomas, but its molecular network regulatory mechanism is still unclear. In this study, we found that KB-1460A1.5 can induce ferroptosis in glioma and enhance sensitivity to RSL3, a ferroptosis inducer. Tandem mass tag proteomics and nontargeted metabolomics suggest that KB-1460A1.5 affects polyunsaturated fatty acid metabolic processes. Gas chromatography-mass spectrometry-based medium- and long-chain fatty acid-targeted metabolomics confirmed that upregulation of KB-1460A1.5 decreased the levels of monounsaturated fatty acids, oleic acid (OA) and palmitoleic acid (PO) in glioma cells. The addition of OA and PO restored KB-1460A1.5-induced cellular ferroptosis. Molecularly, KB-1460A1.5 inhibited the mammalian target of rapamycin signalling pathway to suppress the expression of downstream sterol regulatory element-binding protein 1 (SREBP-1), thereby attenuating the stearoyl-CoA desaturase-1 (SCD1)-mediated desaturation of polyunsaturated fatty acids. Finally, an animal model of subcutaneous glioma confirmed that KB-1460A1.5 could inhibit tumour progression, SREBP-1/SCD1 expression and ferroptosis. In conclusion, increasing the expression level of KB-1460A1.5 in glioma can promote the induction of oxidative stress and ferroptosis in cancer cells through SREBP-1/SCD1-mediated adipogenesis, demonstrating therapeutic potential in preclinical models.


Assuntos
Ácidos Graxos Insaturados , Ferroptose , Glioma , RNA Longo não Codificante , Estearoil-CoA Dessaturase , Proteína de Ligação a Elemento Regulador de Esterol 1 , Serina-Treonina Quinases TOR , Ferroptose/genética , RNA Longo não Codificante/genética , Glioma/patologia , Glioma/metabolismo , Glioma/genética , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Humanos , Animais , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Transdução de Sinais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico
2.
Cell Mol Neurobiol ; 44(1): 36, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637346

RESUMO

Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.


Assuntos
Lesões Encefálicas , Armadilhas Extracelulares , Animais , Ratos , Encéfalo , Lesões Encefálicas/tratamento farmacológico , Ácido Ascórbico , Desoxirribonuclease I/farmacologia
3.
Neurosurg Rev ; 47(1): 32, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182923

RESUMO

The purpose of this study was to investigate the application and efficacy analysis of in situ interposition bypass in complex intracranial aneurysms. This study retrospectively analyzed the clinical data of 21 patients with complex intracranial aneurysms treated with in situ interposition bypass grafting in the Department of Neurosurgery at Tianjin Huanhu Hospital from June 2015 to December 2022. The aneurysms were located in the middle cerebral artery in 16 cases, the anterior cerebral artery in 3 cases, the posterior cerebral artery in 1 case, and the posterior inferior cerebellar artery in 1 case. The interposition graft vessels were taken from the radial artery in 15 cases, the superficial temporal artery in 5 cases, and the occipital artery in 1 case. All patients underwent end-to-end anastomosis with in situ interposition bypass after aneurysm resection, including 13 cases of "I-shaped" type, 5 cases of "V-shaped" type, and 3 cases of "Y-shaped" type. Postoperative digital subtraction angiography (DSA) or computed tomography angiography (CTA) reviews were performed for all the patients, and modified Rankin Scale (mRS) score was used to assess patient prognosis. Three patients developed postoperative basal ganglia infarction and two of them recovered well. One case developed transient incomplete aphasia and one case developed mild hemiparesis, which recovered well after 3 months. The remaining 16 patients did not develop new neurological deficits. Postoperative DSA or CTA showed that the anastomosis of the bypass graft and the graft vessels were patent, and all aneurysms were completely eliminated. Regular postoperative follow-up ranged from 3 to 89 months, and no aneurysm recurred. The percentage of patients with mRS ≤ 2 at the final follow-up was 90.5%. Based on the experience of surgical treatment in our center, in situ interposition bypass technique is a safe and effective option for the treatment of some complex intracranial aneurysms.


Assuntos
Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Procedimentos Neurocirúrgicos , Angiografia Digital , Artéria Cerebral Média
4.
Neurosurg Rev ; 47(1): 138, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578572

RESUMO

Vertebrobasilar artery dissecting aneurysms (VBDAs) are the most surgically challenging type of aneurysm. Cerebral revascularization is the ultimate treatment for complex VBDAs. We retrospectively analysed the characteristics, surgical outcomes and follow-up data of 21 patients who underwent cerebral revascularization to treat complex VBDAs from 2015 to 2022. According to the location of the aneurysm and the anatomic relationship between the VBDA and the PICA, VBDA patients were classified into four groups: aneurysms located at the VA with PICA involvement (10 patients), aneurysms located at the VA without PICA involvement (1 patient), aneurysms located at the basilar apex segment (1 patient) and aneurysms located at the basilar trunk segment (9 patients). A surgical algorithm for complex VBDAs was determined primarily by the location of the aneurysm, the status of the aneurysm and the ability of retrograde blood flow to reach the proximal vertebrobasilar artery. Surgical modalities for patients with aneurysms in the VA with PICA involvement included low-flow (OA-PICA) bypasses with aneurysm trapping, aneurysm excision or reconstructive clip in 8 patients and STA-PCA bypass combined with PICA preservation and aneurysm trapping in 2 patients. In patients with aneurysms in the VA without PICA involvement, aneurysm excision was performed without cerebral bypass. In patients with aneurysms in the basilar apex segment, high-flow bypass (ECA-RA-P2) with aneurysm trapping was performed. In patients with aneurysms in the basilar trunk segment, surgical modalities included high-flow bypasses (ECA-RA-P2 and LVA-RA-P2) with aneurysm trapping or proximal occlusion in 6 patients, ECA-RA-P2 bypass with partial proximal occlusion in 1 patient, ECA-RA-P2 bypass alone in 1 patient, and STA-PCA bypass with R-VA narrowing in 1 patient. Of the 21 patients, 20 experienced clinical improvement or no change, and 17 of 21 patients achieved favourable functional outcomes (mRS ≤ 2). However, one patient died of infarction and respiratory failure postoperatively. Aneurysms were completely obliterated in 13 patients, shrank in 5 patients and stabilized in 2 patients. The median follow-up period was 32.5 months. During the follow-up period, all bypasses were patent, and further clinical improvement was observed in 11 patients. Cerebral revascularization appears to be safe and effective for the treatment of complex VBDAs, and cerebral revascularization could act as a complementary treatment strategy.


Assuntos
Revascularização Cerebral , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Procedimentos Neurocirúrgicos , Artérias , Resultado do Tratamento
5.
Acta Neurochir (Wien) ; 166(1): 275, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910196

RESUMO

PURPOSE: The purpose of this study was to describe the effectiveness and evaluation of open surgical treatment of basilar artery aneurysms in the context of interventional therapy era, including surgical clipping and blood reconstruction, by retrospectively analyzing the clinical data of basilar artery aneurysms in our center. METHODS: Patients with basilar artery aneurysms who were treated at our center were retrospectively included according to the inclusion and exclusion criteria. The basic clinical data, surgical approach, clinical follow-up and prognosis of the enrolled patients were analyzed in detail. In this study, the mRS score was applied to assess the neurological prognosis of the patients, and the relevant data were statistically analyzed using SPSS. RESULTS: A total of 104 eligible patients treated at our center from January 2010 to August 2023 were included in this study, of which 67 were treated by open surgery and 37 by bypass. For the 67 patients with open surgical clipping, the mean age was 60.0 (52.0, 65.0) years. The maximum diameter of the aneurysms ranged from 2.0 mm to 54.0 mm, with a mean of 13.9 (10.0, 19.0) mm. The mean follow-up time was 38 (20, 58) months. At the last follow-up, 61 (91.0%) completely obliterated aneurysms and 6 (9.0%) incompletely obliterated aneurysms were found. The prognosis was good in 59 (88.1%) patients and poor in 8 (11.9%). After surgical clipping, the difference between complete and incomplete postoperative aneurysm elimination was statistically significant between the favorable and poor prognosis groups (P < 0.001). For the 37 bypass group patients, the mean age was 52.0 (45.5, 59.0) years. The maximum diameter of the aneurysm ranged from 10.5 mm to 55.0 mm, with a mean of 28.55 ± 12.08 mm. Bypass combined with proximal occlusion was performed in 18 (48.6%) patients, and bypass only was performed in 19 (51.4%) patients. Clinical follow-up was 19.0 (10.5, 43.0) months. There were 19 (51.4%) patients with complete elimination of the aneurysm, 13 (35.1%) with incomplete elimination of the aneurysm, and 5 (13.5%) with aneurysm stabilization. The prognosis was good in 32 (86.5%) patients and poor in 5 (13.5%) patients. CONCLUSION: Treatment of basilar artery aneurysms is challenging. In the context of the rapidly evolving interventional therapy era, open surgery including surgical clipping and bypass is an ideal option for complex basilar artery aneurysms not amenable to intervention.


Assuntos
Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos , Seguimentos , Artéria Basilar/cirurgia , Adulto
6.
J Craniofac Surg ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38227639

RESUMO

OBJECTIVE: To investigate the clinical characteristics and treatment strategy of anterior circulation aneurysm presenting with cerebral ischemia. METHODS: We performed a retrospective review of patients with intracranial anterior circulation aneurysms presenting with cerebral ischemia examined in the Fifth Ward of the Neurosurgery Department of Tianjin Huanhu Hospital between September 2016 and September 2023. Data were reviewed for age, sex, presentation, type and size, location, treatment modalities, postoperative complications, clinical and imaging outcomes, and follow-up outcomes. RESULTS: Among the 13 patients, there were 8 males and 5 females (1.6:1). Their presentations included ischemic stroke (69.23%, 9/13) and transient ischemic attack (TIA) (30.77%, 4/13). The aneurysms were dissecting (46.15%, 6/13), saccular (30.77%, 4/13), and saccular combined with thrombosis (23.08%, 3/13) in shape. There were 6 giant aneurysms, 4 large aneurysms, and 3 microaneurysms. Three (23.08%, 3/13) aneurysms were located at the internal carotid artery (ICA) and 10 (76.92%, 10/13) were located in the middle cerebral artery (MCA). A preoperative magnetic resonance perfusion (MRP) examination was performed in all patients, and 9 (69.23%, 9/13) patients showed hypoperfusion. Treatment modalities included stent-assisted embolization, direct clipping, clipping combined with bypass, resection combined with bypass, isolated combined with bypass, proximal occlusion combined with bypass, and the internal carotid artery constriction combined with bypass. Twelve (92.31%, 12/13) patients had no postoperative complications, and temporary complications occurred in 1 (7.69%, 1/13) patient. Aneurysms disappeared in 11 cases and shrank in 2 cases postoperatively. All patients were followed up for 1 to 72 months. We found no new cerebral infarction, no subarachnoid hemorrhage, and no recurrence or enlargement of aneurysms during the follow-up. CONCLUSIONS: Intracranial anterior circulation aneurysm presenting with cerebral ischemia is rare. Saccular aneurysms with wide neck or thrombosis and dissected aneurysms of the anterior circulation may result in cerebral ischemic attack caused by distal vascular embolism. Individualized treatment should be performed, and cerebral revascularization is an effective treatment for patients with intracranial anterior circulation aneurysms presenting with cerebral ischemia.

7.
J Craniofac Surg ; 35(1): e60-e66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37948620

RESUMO

BACKGROUND: Pineal region lesions are more common in children than adults; however, therapeutic strategies for pineal region lesions in children are controversial. METHODS: A retrospective study involving 54 pediatric with pineal region lesions was conducted. The therapeutic strategies for lesions and hydrocephalus were classified and analyzed. RESULTS: Radiotherapy of pineal region lesions was shown to result in better postoperative recovery and fewer complications in the short-term compared with lesion resection. Total resection was related to smaller lesion size, endoscopic procedures, and a better prognosis. Cerebrospinal fluid (CSF) diversion before the resection reduced hydrocephalus recurrences, whereas further lesion resection had a negative short-term influence on CSF diversion. Among the 4 therapeutic strategies to manage hydrocephalus, a third ventriculostomy (ETV) was reasonable and further resection did not have a negative impact on the ETV. The relief of hydrocephalus was also related to better postoperative recovery, a higher total resection rate, fewer complications, and a better prognosis. Logistical regression analysis indicated that lesion size and intracranial complications were predictors of outcome. CONCLUSIONS: For lesion treatment, total resection and radiotherapy are essential components in children. Total resection and CSF diversion before resection were beneficial, whereas further lesion resection had a negative impact on CSF diversion. For hydrocephalus treatment, ETV was shown to be the best therapeutic strategy for management of pediatric hydrocephalus. Total resection and better preoperative health status were associated with greater hydrocephalus relief. For the overall prognosis, a lack of hydrocephalus relief was associated with poor outcomes. Lesion size and intracranial complications may be the best predictors of outcome.


Assuntos
Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Adulto , Criança , Humanos , Terceiro Ventrículo/cirurgia , Estudos Retrospectivos , Ventriculostomia/efeitos adversos , Ventriculostomia/métodos , Hidrocefalia/cirurgia , Hidrocefalia/etiologia , Derivação Ventriculoperitoneal/efeitos adversos , Resultado do Tratamento , Neuroendoscopia/métodos
8.
J Craniofac Surg ; 35(4): 1057-1061, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363290

RESUMO

BACKGROUND: Occipital artery (OA) acts as a vital donor vessel in intra-cranialand extra-cranial bypass. Ultrasonography and digital subtracted angiography (DSA) are becoming increasingly important in the assessment of vascular morphology and hemodynamically; however, quantitative analysis of occipital artery bypass donor vessels by Ultrasonography and DSA are seldom discussed. METHODS: A retrospective study involving 62 cases accepted occipital artery bypass to treat posterior circulation aneurysms or artery occlusion/stenosis. The characteristics of OA are collected and analyzed. RESULTS: Occipital artery bypasses were performed to treat posterior circulation aneurysms in 34 patients and to treat posterior circulation artery occlusion or stenosis in 28 patients. Compared with the ultrasonography group, the DSA group had a greater diameter of OA, and Bland Altman analysis indicated that the discrepancy between the 2 groups was about 0.555 mm. Ultrasonography showed the characteristics of OA: the mean Peak Systolic Velocity (PSV) was 42.98 cm/s, the mean End Diastolic Velocity (EDV) was 8.811 cm/s, and the mean Resistance Index (RI) was 1.46. There were no statistical differences in the diameter of OA, PSV, EDV, and RI between the male group and female group, the elderly group and younger adult group or the left occipital artery group and right occipital artery group. However, compared with patients with posterior circulation aneurysms, patients with artery occlusion or stenosis were older and had higher PSV, RI, and greater diameter in occipital arteries. The mean diameter of occipital arteries was increased in the first postoperative years but reduced in 3 patients during 1 year follow-up. CONCLUSIONS: Both ultrasonography and DSA were effective assessment methods of occipital artery bypasses, and the DSA group had a greater diameter of OA. Age, gender, and left or right sides had little effect on the diameter of OA, PSV, EDV, and RI. Posterior circulation occlusion or stenosis had higher PSV, RI, and greater diameter of the occipital artery when compared with posterior circulation aneurysms. Occipital artery bypasses could increase the diameter of OA in most cases.


Assuntos
Angiografia Digital , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Revascularização Cerebral/métodos , Ultrassonografia/métodos , Resultado do Tratamento
9.
J Craniofac Surg ; 35(4): 1152-1156, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38743286

RESUMO

OBJECTIVE: To explore how to effectively manage the residual or recurrent intracranial aneurysms after embolization. METHODS: The authors retrospectively reviewed our experience of endovascular interventional therapy, surgical clipping, and cerebrovascular bypass surgery in the treatment of residual or recurrent aneurysms after embolization at the authors' institution from 2018 to 2022. RESULTS: The Glasgow Outcome Scale of 28 patients after the procedure and at discharge showed that 24 recovered well, 3 had severe disability, and 1 died. During the 24-month follow-up, 26 had a good recovery, 1 suffered from disability, and 1 died. Two cases of aneurysm recurrence were detected, and both were treated through endovascular therapy. Among them, 1 case underwent a repeat endovascular embolization, and 1 case was switched to surgical clipping. No residual aneurysms were observed in the remaining patients who underwent bypass surgery, and their bypass grafts were all patent. CONCLUSION: Based on the clinical status of patients, aneurysmal characteristics, surgical risk, and possibility of rerupture of aneurysms, an individualized strategy was proposed for residual or recurrent aneurysms after embolization. The use of endovascular interventional therapy or surgical clipping can be safely and effectively managed, and cerebrovascular bypass surgery can effectively manage complex aneurysms.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Recidiva , Humanos , Aneurisma Intracraniano/cirurgia , Embolização Terapêutica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Procedimentos Endovasculares/métodos , Idoso , Resultado do Tratamento , Escala de Resultado de Glasgow
10.
J Craniofac Surg ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958949

RESUMO

OBJECTIVE: To compare the range of endoscopic and microscopic exposure of the petroclival core area through the middle skull base and to observe the corresponding anatomical structures. METHODS: Ten intact adult cadaveric head specimens fixed with formaldehyde were craniotomized through an expanded middle skull base epidural approach on 20 sides. The distance from the greater superficial petrosal nerve to the petrous ridge was measured. When different degrees (1-3 degrees) of the Kawase triangle bone were removed, the exposed anatomical structure was observed, and the exposed core area of the rock slope was measured under an endoscope and microscope. RESULTS: The average distance from the greater superficial petrosal nerve to the petrous ridge was 14.26 mm. During 1 to 2 degrees of bone removal, the petrous segment of the internal carotid artery (ICA) was not exposed, whereas during 3 degrees of bone removal, the petrous segment of the ICA was exposed. At 1 degree of bone removal, 400.62 ± 15.73 mm2 of the area was exposed by endoscopy and 170.87 ± 8.93 mm2 by microscopy, and the abducens nerve was not exposed. However, there was a significant difference between the two areas (P < 0.001). During 2 degrees of bone removal, 689.30 ± 32.06 mm2 of the abducens nerve was exposed by endoscopy, but 366.84 ± 30.30 mm2 of the abducens nerve could not be exposed by microscopy; moreover, there was a significant difference in the area of exposure between the two (P < 0.001). At 3 degrees of bone removal, the endoscopic exposure area was 875.92 ± 31.87 mm2, the microscopic exposure area was 699.26 ± 48.00 mm2, and the abducens nerves were exposed. There were significant differences between the two areas (P < 0.001). However, the difference between the 2-degree endoscopic exposure area and the 3-degree microscopic exposure area was studied by using paired t tests, and there was no difference (P > 0.05). CONCLUSION: When the same degree of the Kawase triangle bone was removed, the extent of endoscopic exposure of the petroclival core area was significantly greater than the extent of microscopic exposure. At 2 degrees of bone removal, an endoscopic application can maximally expose the petroclival core area, thus reducing the probability of exposure damage to the ICA and abductor nerve.

11.
Clin Immunol ; 256: 109772, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37716612

RESUMO

BACKGROUND: In our previous study, we found for the first time that temozolomide (TMZ), the first-line chemotherapeutic agent for glioblastoma (GBM), can generate a large amount of reactive oxygen species (ROS) under ultrasound irradiation. Sonodynamic therapy (SDT) using TMZ as the sonosensitizer produced more potent antitumor effects than TMZ alone. Here, we further evaluate the effects of TMZ-based SDT on subcellular structures and investigate the immunogenic cell death (ICD)-inducing capability of TMZ-based SDT. METHODS: The sonotoxic effects of TMZ were explored in LN229 and GL261 glioma cells. The morphology of endoplasmic reticulum and mitochondria was observed by transmission electron microscopy. The nuclear DNA damage was represented by γ-H2AX staining. Bone marrow-derived dendritic cells (BMDCs) were employed to assess ICD-inducing capability of TMZ-based SDT. A cyclic arginine-glycine-aspartic (c(RGDyC))-modified nanoliposome drug delivery platform was used to improve the tumor targeting of SDT. RESULTS: TMZ-based SDT had a greater inhibitory effect on glioma cells than TMZ alone. Transmission electron microscopy revealed that TMZ-based SDT caused endoplasmic reticulum dilation and mitochondrial swelling. In addition, endoplasmic reticulum stress response (ERSR), nuclear DNA damage and mitochondrial permeability transition pore (mPTP) opening were promoted in TMZ-based SDT group. Most importantly, we found that TMZ-based SDT could promote the "danger signals" produced by glioma cells and induce the maturation and activation of BMDCs, which was associated with the mitochondrial DNA released into the cytoplasm in glioma cells. In vivo experiments showed that TMZ-based SDT could remodel glioma immune microenvironment and provoke durable and powerful anti-tumor immune responses. What's more, the engineered nanoliposome vector of TMZ conferred SDT tumor targeting, providing an option for safer clinical application of TMZ in combination with SDT in the future. CONCLUSIONS: TMZ-based SDT was capable of triggering ICD in glioma. The discovery of TMZ as a sonosensitizer have shown great promise in the treatment of GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Morte Celular Imunogênica , Apoptose , Glioma/tratamento farmacológico , Glioblastoma/patologia , Linhagem Celular Tumoral , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Microambiente Tumoral
12.
BMC Cancer ; 23(1): 989, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848823

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are considered key players in the formation and development of tumors. Herein, Gene Expression Profiling Interactive Analysis (GEPIA) was employed as a bioinformatics technology. LINC02587 is differentially expressed in bladder urothelial cancer, glioblastoma, lung adenocarcinoma, lung SCC, melanoma, and other tumor tissue and cells. However, its impact on the emergence of glioma and its mechanism is remaining elusive. METHODS: Some of the in vitro assays employed in this study were the CCK-8 / Annexin-V / Transwell assays, colony formation, and wound healing, together with Western blot (WB) evaluation. MSP / BSP assays were employed for assessing the CpG island's methylation status in the LINC02587 promoter. Through transcriptome, ferroptosis-related experiments, and WB evaluation, it was confirmed that LINC02587 is correlated with the regulation of ferroptosis in tumor cells, and CoQ-Fsp1 is one of its regulatory pathways. Moreover, the underlined in-vitro results were further validated by in-vivo studies. RESULTS: The current study shows that the promoter sequence of LINC02587 is regulated by methylation. The silencing of LINC02587 can inhibit cellular proliferative, migrative, and invasive properties, and induce ferroptosis within gliomas through the CoQ-FSP1 pathway. CONCLUSIONS: LINC02587 is likely to be a novel drug target in treating glioma.


Assuntos
Ferroptose , Glioblastoma , Glioma , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Metilação de DNA , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioma/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
13.
Neurosurg Rev ; 46(1): 192, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37540310

RESUMO

The purpose of this research was to demonstrate the effectiveness and clinical outcome of an external carotid artery-radial artery graft-posterior cerebral artery (ECA-RAG-PCA) bypass in the treatment of complex vertebrobasilar artery aneurysms (VBANs) in a single-center retrospective study. An ECA-RAG-PCA bypass may be a last and very important option in the treatment of complex VBANs when conventional surgical clipping or endovascular interventions fail to achieve the desired outcome. This study retrospectively analyzed the clinical presentation, case characteristics, aneurysm location, size and morphology, choice of surgical strategy, complications, clinical follow-up, and prognosis of the patients enrolled. The data involved were analyzed by the appropriate statistical methods. A total of 24 patients with complex VBANs who met the criteria were included in this study. Eighteen (75.0%) were male and the mean age was 54.1 ± 8.83 years. The aneurysms were located in the vertebral artery, the basilar artery, and in the vertebrobasilar artery with simultaneous involvement. All patients underwent ECA-RAG-PCA bypass surgery via an extended middle cranial fossa approach, with 8 (33.3%) undergoing ECA-RAG-PCA bypass only, 3 (12.5%) undergoing ECA-RAG-PCA bypass combined with aneurysm partial trapping, and 12 (50.0%) undergoing ECA-RAG-PCA bypass combined with proximal occlusion of the parent artery. The average clinical follow-up was 22.0 ± 13.35 months. The patency rate of the high-flow bypass was 100%. At the final follow-up, 15 (62.5%) patients had complete occlusion of the aneurysm, 7 (29.2%) patients had subtotal occlusion of the aneurysm, and 2 (8.3%) patients had stable aneurysms. The rate of complete and subtotal occlusion of the aneurysm at the final follow-up was 91.7%. The clinical prognosis was good in 21 (87.5%) patients and no procedure-related deaths occurred. Analysis of the good and poor prognosis groups revealed a statistically significant difference in aneurysm size (P = 0.034, t-test). Combining the results of this study and the clinical experience of our center, we propose a surgical algorithm and strategy for the treatment of complex VBANs.The technical approach of ECA-RAG-PCA bypass for complex VBANs remains important, even in an era of rapid advances in endovascular intervention. When conventional surgical clipping or endovascular intervention has failed, an ECA-RAG-PCA bypass plays a role that cannot be abandoned and is a very important treatment option of last resort.


Assuntos
Revascularização Cerebral , Aneurisma Intracraniano , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Artéria Cerebral Posterior/cirurgia , Estudos Retrospectivos , Aneurisma Intracraniano/cirurgia , Artéria Radial/cirurgia , Artéria Carótida Externa/cirurgia , Revascularização Cerebral/métodos , Resultado do Tratamento
14.
Neurosurg Rev ; 46(1): 293, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37924361

RESUMO

To explore the treatments for and manifestations of carotid blowout syndrome (CBS) and to further explore the critical role of high-flow bypass combined with parent artery isolation. The clinical data of nine patients with radiotherapy-related CBS who were admitted to our hospital from March 2020 to March 2023 were retrospectively analyzed. Relevant literature was reviewed. From March 2020 to March 2023, nine CBS patients were admitted to Tianjin Huanhu Hospital, including eight males and one female. Digital subtraction angiography was performed for all the patients; all the pseudoaneurysms were located at the petrous segment of the internal carotid artery. A balloon occlusion test was performed on four patients, which was tolerated by all patients. CT and MRI scans showed seven cases of osteonecrosis combined with infection and two cases of tumor recurrence. Emergency permanent parent artery occlusion was performed on six patients, aneurysm embolization was completed in one case, covered stent implantation was performed in one patient, and three cases were treated by cerebral bypass surgery (including two patients with failed interventional treatment). Rebleeding was found in two patients, and no rebleeding was found in the bypass group. Paralysis was found in three patients, and asymptomatic cerebral infarction without permanent neurologic impairment was found in three patients. Two patients died due to tumor progression. Emergency occlusion surgery is lifesaving in the acute phase of CBS. Endovascular therapy cannot prevent the progression of pseudoaneurysms or lower the recurrence rate of bleeding events. High-flow bypass combined with parent artery isolation is a safe and effective method that may facilitate further surgical treatment. Further research is warranted.


Assuntos
Falso Aneurisma , Doenças das Artérias Carótidas , Embolização Terapêutica , Neoplasias de Cabeça e Pescoço , Masculino , Humanos , Feminino , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/cirurgia , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Artérias Carótidas , Embolização Terapêutica/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Stents , Resultado do Tratamento
15.
Neurosurg Rev ; 46(1): 122, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37191817

RESUMO

This study aimed to investigate the clinical characteristics of intracranial aneurysms in young adults and summarize our treatment experiences. We performed a retrospective review of young patients (15-24 years old) with intracranial aneurysms examined in the Fifth Ward of the Neurosurgery Department of Tianjin Huanhu Hospital between January 2015 and November 2022. Data was reviewed for age, sex, presentation, type and size, treatment modalities, location, postoperative complications, and clinical and imaging outcomes. Among the 23 patients, there were 11 males and 12 females (1:1.09). Their presentations included headache, neurological deficits, aneurysmal subarachnoid hemorrhage, incidental or asymptomatic aneurysm, and traumatic subarachnoid hemorrhage. Twenty-five cases of intracranial aneurysms in 25 patients were identified. The aneurysms were saccular (32%, 8/25), dissecting (52%, 13/25), and fusiform (16%, 4/25) in shape. Treatment modalities included direct clipping, embolization, bypass, trapping, resection, coarctation of internal carotid artery (ICA), and endovascular vessel sacrifice. Of the 25 aneurysms, 16 (64%, 16/25) aneurysms were located in anterior circulation, and 9 (36%, 9/25) were located in the posterior circulation, while multiple aneurysms were identified in two patients. A preoperative magnetic resonance perfusion (MRP) examination was performed in 15 patients with unruptured complex aneurysms, of whom 13/15 (86.67%) showed hypoperfusion. Eighteen (78.26%, 18/23) patients had no postoperative complications, temporary complications occurred in 4 (17.39%, 4/23) patients, and 1 patient died postoperatively. The intracranial aneurysms in young adults (15 ~ 24 years old) are rare. The posterior circulation is more commonly involved than adults, giant and huge aneurysms are frequent, and fusiform and dissecting pathologic features are common. Headache is the most common clinical manifestation. Individualized treatment should be performed, and bypass is an effective treatment for young patients with intracranial aneurysms.


Assuntos
Revascularização Cerebral , Embolização Terapêutica , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Masculino , Feminino , Humanos , Adulto Jovem , Adolescente , Adulto , Aneurisma Intracraniano/diagnóstico , Resultado do Tratamento , Revascularização Cerebral/métodos , Hemorragia Subaracnóidea/cirurgia , Embolização Terapêutica/métodos , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos
16.
Neurosurg Rev ; 46(1): 68, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36917348

RESUMO

Cerebral revascularization is the ultimate treatment for a subset of complex middle cerebral artery (MCA) aneurysms. The decision for the revascularization strategy should be made during the treatment process. This study aimed to summarize the revascularization strategies for different types of complex MCA aneurysms and their outcomes. The clinical data of patients with complex MCA aneurysms who underwent cerebral revascularization since 2015 were analyzed retrospectively. The aneurysms were classified according to the location and other main characteristics that affect the selection of surgical modalities. The corresponding surgical modalities and treatment outcomes were summarized. A total of 29 patients with 29 complex MCA aneurysms were treated with cerebral revascularization from 2015 to 2022. Treated aneurysms were located at the prebifurcation segment in 7 patients, bifurcation segment in 12 patients, and postbifurcation segment in 10 patients. Surgical modalities in the prebifurcation segment included four high-flow extracranial-to-intracranial (EC-IC) bypasses with aneurysm trapping or proximal occlusion, two IC-IC bypasses with aneurysm excision, and one combination bypass with aneurysm excision. In the bifurcation segment, surgical modalities included two low-flow EC-IC bypasses with aneurysm excision or trapping, six IC-IC bypasses with aneurysm excision, three combination bypasses with aneurysm excision, and one constructive clipping with IC-IC bypass. In the postbifurcation segment, surgical modalities included nine IC-IC bypasses with aneurysm excision and low-flow EC-IC bypass with aneurysm trapping. The revascularization strategy for prebifurcation aneurysms was determined based on the involvement of lenticulostriate arteries, whereas the strategy for bifurcation aneurysms was determined based on the number of distal bifurcations and the shape of the aneurysm. The location of the aneurysm determined the revascularization strategy for aneurysms in the postbifurcation segments. Angiography demonstrated that aneurysms were completely obliterated in 26 cases and shrank in 3 cases, and all bypasses except one were patent. The mean follow-up period was 47.5 months. Three patients developed hemiplegic paralysis, and one developed transient aphasia postoperatively due to cerebral ischemia. No new neurological dysfunction occurred in the other 25 patients with no recurrence or enlargement of aneurysms during the follow-up. Prebifurcation aneurysms involving the lenticulostriate arteries require proximal occlusion with high-flow bypass. Most of the other aneurysms can be safely excised or trapped by appropriate revascularization strategies according to their location and orientation.


Assuntos
Revascularização Cerebral , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Neurocirúrgicos , Artéria Cerebral Média/cirurgia
17.
J Craniofac Surg ; 34(6): 1884-1887, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37418620

RESUMO

OBJECTIVE: To explore the methods of protecting the external branch of the superior laryngeal nerve during carotid endarterectomy through microsurgical anatomic study of the external branch of the superior laryngeal nerve in cadaveric specimens. METHODS: A total of 30 cadaveric specimens (60 sides) were dissected to measure the thickness of the external branch of the superior laryngeal nerve. A triangular area was exposed, bounded by the lower border of the digastric muscle superiorly, the medial edge of the sternocleidomastoid muscle laterally, and the upper border of the superior thyroid artery inferiorly. The probability of the occurrence of the external branch of the superior laryngeal nerve in this area was observed and recorded. The distance among the midpoint of the external branch of the superior laryngeal nerve in this area with the tip of the mastoid process and the angle of the mandible as well as the bifurcation of the common carotid artery was measured and recorded. RESULTS: Among 30 specimens of cadaveric heads (60 sides) examined 53 external branches of the superior laryngeal nerve were observed while 7 were absent. Of the 53 branches observed, 5 were located outside the anatomic triangle region mentioned above, while the remaining 48 branches were located within the anatomic triangle region with a probability of ~80%. The thickness of the midpoint of the external branches of the superior laryngeal nerve within the anatomic triangle region was 0.93 mm (0.72-1.15 mm [±0.83 SD]), located 0.34 cm [-1.62-2.43 cm (±0.96 SD)] posterior to the angle of the mandible, 1.28 cm (-1.33 to 3.42 cm (±0.93 SD)] inferiorly; 2.84 cm (0.51-5.14 cm±1.09 SD) anterior to the tip of the mastoid process, 4.51 cm (2.82-6.39 cm±0.76 SD) inferiorly; 1.64 cm [0.57-3.78 cm (±0.89 SD)] superior to the bifurcation of the carotid artery. CONCLUSIONS: During carotid endarterectomy procedure, using the cervical anatomic triangle region, as well as the angle of the mandible, the tip of the mastoid process, and the bifurcation of the carotid artery as anatomic landmarks, is of significant clinical importance for protecting the external branches of the superior laryngeal nerve.


Assuntos
Endarterectomia das Carótidas , Humanos , Pescoço/cirurgia , Nervos Laríngeos/anatomia & histologia , Nervos Laríngeos/cirurgia , Artérias Carótidas , Cadáver
18.
J Craniofac Surg ; 34(2): e182-e186, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36036515

RESUMO

OBJECTIVES: The formation of vulnerable carotid artery plaque may be closely related to a single factor or caused by multiple factors. This paper discusses the pathogenic risk factors for vulnerable plaque in patients with severe internal carotid artery (ICA) stenosis who received endarterectomy through regression analysis. MATERIALS AND METHODS: A total of 98 patients with a complete clinical and laboratory assessment underwent carotid endarterectomy. Metabolic syndrome (MetS) and MetS components, ICA plaque thickness and ICA peak systolic velocity, previous ischemic stroke or transient ischemic attack (TIA), and other risk factors were included in the pathogenic risk factor for vulnerable plaque. Univariate logistic regression analysis was used to determine vulnerable carotid plaque risk factors. If P <0.2, it was considered potential confounders. Binary logistic regression model was controlled for potential confounders. RESULTS: Among the 98 patients, stable carotid plaques 38 (39%) and unstable carotid plaques 60 (61%), male 76 (77.6%) and female 22 (22.4%), and Han Chinese 68 (68.4%) and Mongols 30 (30.6%). Univariate logistic regression to P <0.2 has 6 risk factors, which are previous ischemic stroke or TIA, ICA peak systolic velocity, ICA plaque thickness, body mass index, total cholesterol, and alcohol consumption. The significant result of the binary logistic regression analysis was the previous ischemic stroke or TIA (OR=4.52; 95% CI, 1.67-12.09), P =0.003 and ICA peak systolic velocity (OR=1.01; 95% CI, 1.00-1.02), P =0.014. CONCLUSIONS: The patients with previous ischemic stroke or TIA and higher ICA peak systolic velocity are associated with vulnerable plaque pathogenic features. There is no obligatory association between MetS and formation of carotid plaque vulnerability.


Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/etiologia , Artérias Carótidas , Estenose das Carótidas/complicações , Fatores de Risco , AVC Isquêmico/complicações , Artéria Carótida Interna/patologia
19.
JAMA ; 330(8): 704-714, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37606672

RESUMO

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.


Assuntos
Arteriosclerose , Revascularização Cerebral , Ataque Isquêmico Transitório , Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arteriosclerose/complicações , Arteriosclerose/diagnóstico por imagem , Arteriosclerose/cirurgia , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/métodos , Revascularização Cerebral/mortalidade , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/cirurgia , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/cirurgia , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/cirurgia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/mortalidade , AVC Isquêmico/cirurgia , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/cirurgia , Imagem de Perfusão , Método Simples-Cego , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/cirurgia , Tomografia Computadorizada de Emissão , Inibidores da Agregação Plaquetária/uso terapêutico , Terapia Combinada
20.
Eur Neurol ; 85(6): 478-485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35764062

RESUMO

INTRODUCTION: The level of collateral compensation plays a pivotal role in chronic symptomatic intracranial vertebrobasilar stenosis (IVBS). This study aimed to evaluate the association between cerebrovascular risk factors and collateral compensation in chronic symptomatic IVBS. METHODS: This single-center cross-sectional study retrospectively reviewed 238 patients with angiographically demonstrated IVBS and divided them into good collateral compensation (GCC) group (collateral grade: 3-4, n = 110) and poor collateral compensation (PCC) group (collateral grade: 0-2, n = 128). The demographic information, laboratory tests, and clinical data of the two groups were compared and assessed using univariate logistic regression. Multivariate logistic regression was employed to analyze the independent related factors of collateral compensation. RESULTS: Hyperlipidemia, high-density lipoprotein (HDL), and fasting blood glucose (FBG) were significantly different between the two groups. Multivariate logistic regression analysis revealed that HDL (odds ratio [OR]: 1.134, 95% confidence interval [CI]: 1.081-1.190), FBG (OR: 0.945, 95% CI: 0.925-0.964), and hyperlipidemia (OR: 0.261, 95% CI: 0.129-0.527) were statistically independent related factors of collateral compensation. The receiver-operating characteristic (ROC) analysis provided cutoff values of 34 mg/dL and 135 mg/dL for HDL and FBG associated with GCC and PCC. CONCLUSION: Higher HDL levels are associated with higher incidence of GCC, whereas higher FBG levels and hyperlipidemia are associated with higher incidence of PCC.


Assuntos
Circulação Colateral , Humanos , Constrição Patológica/diagnóstico por imagem , Estudos Retrospectivos , Estudos Transversais , Fatores de Risco
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