BACKGROUND/AIM:Endoplasmic reticulum resident protein 44 (ERP44), a protein disulfide isomerase family member, has been implicated in tumor biology, but its role in lower-grade glioma (LGG) remains unclear. This study investigated the prognostic significance and biological function of ERP44 in LGG, focusing on proliferation and temozolomide (TMZ) resistance. MATERIALS AND METHODS:ERP44 expression, clinicopathological associations, and prognostic value were analyzed using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) datasets. Time-dependent receiver operating characteristic (ROC) curves, Cox regression, and a prognostic nomogram were constructed. Differential expression, Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) enrichment, immune infiltration, and drug sensitivity analyses were performed. Functional validation was conducted in SW1088 and SW1783 cells using shRNA-mediated ERP44 knockdown, followed by RT-qPCR, western blotting, CCK-8, colony formation, and TMZ IC50 assays. Subcutaneous xenograft models with or without TMZ treatment were used for in vivo validation. RESULTS:ERP44 was markedly upregulated in LGG and associated with higher WHO grade, IDH wildtype status, 1p/19q non-codeletion, and poor survival in TCGA and CGGA cohorts. ERP44 showed strong prognostic performance and improved risk stratification in a multivariable nomogram. Enrichment analyses linked high ERP44 expression to immune/inflammatory pathways and reduced neuronal functional signatures. ERP44 positively correlated with immune infiltration, proliferation/stemness markers, and predicted TMZ resistance, while its knockdown inhibited proliferation and colony formation, reduced TMZ IC50, suppressed xenograft growth, enhanced TMZ efficacy, and decreased Ki67 positivity. CONCLUSION:ERP44 is a prognostic biomarker that promotes LGG proliferation and TMZ resistance, suggesting its potential as a therapeutic target.
Objective: Access to the pineal region has always represented a formidable challenge to the neurosurgeons. This study aims to explore the surgical techniques of the occipital transtentorial approach (OTA) without using brain retractor for excision of pineal region tumors based on the author’s experience and literature review. Methods: A retrospective analysis was performed of patients who underwent surgery for pineal tumors via OTA using dynamic retraction at our institution from 2018 to 2022. The clinical data, surgical procedure, and results were examined. Results: Twelve patients underwent surgery via OTA for treatment of pineal tumors. In all cases, it was feasible to complete surgery without using brain retractor. Gross total resection was achieved in 10 cases (83.3 %), while subtotal resection in 2 cases (16.7 %). There were no mortalities. Three patients presented with upper gaze palsy after surgery, 2 of them experienced complete recovery at the third month follow-up. Only one patient had residual neurologic deficit. Two patients reported transit diplopia after surgery. No postoperative hemianopsia was observed in this series. Conclusion: The occipital transtentorial approach is effective for the removal of tumors in the pineal region. Dynamic retraction with handheld instruments and meticulous dissection of arachnoid membrane around the deep veins can provide a sufficient working space.
目的 探讨经Dolenc入路手术夹闭基底动脉顶端动脉瘤的手术方法及治疗效果.方法 回顾性分析2014年6月至2022年6月经Dolenc入路手术治疗的26例基底动脉顶端动脉瘤的临床资料.结果 术后2周CTA检查显示26例基底动脉顶端动脉瘤均完全夹闭.术后出现动眼神经麻痹5例、脑积水1例(脑室-腹腔分流术)、偏瘫1例,无脑脊液漏,无手术死亡病例.26例术后随访6~48个月;动眼神经麻痹5例中,术后3个月内完全恢复4例,部分恢复1例;1例脑积水行脑室-腹腔分流术后恢复良好,1例偏瘫恢复生活自理.术后6个月改良Rankin量表评分0分16例,1分3例,2分4例,3分3例;CTA复查未见基底动脉顶端动脉瘤复发,载瘤动脉通畅.结论 显微手术是治疗基底动脉顶端动脉瘤的重要方式,经Dolenc入路手术可获得良好的效果.
约30%~40%的精神疾病患者对药物、心理疗法和其他治疗方式多模式综合治疗后反应不佳或无效,从而进展为难治性精神疾病.神经调控技术运用于治疗难治性精神疾病已有60多年历史.近年来,越来越多的神经影像学研究发现精神疾病发病与神经环路功能障碍有关.内囊前肢(ALIC)是这些神经环路中的关键节点,调控ALIC在治疗强迫症(OCD)、重度抑郁症等精神疾病显得越来越重要,本文就ALIC的解剖学、神经影像学及在难治性精神疾病的运用进展做一综述.
目的 探讨立体定向辅助下双侧内囊前肢毁损术(ALIC-RSF)治疗难治性精神分裂症(SCZ)伴发的攻击行为的疗效.方法 回顾性分析2019年6月至2021年1月立体定向辅助下ALIC-RSF治疗的35例伴攻击行为的难治性SCZ的临床资料.术前、术后3个月、术后1年,使用外显攻击量表(MOAS)、阳性及阴性症状量表(PANSS)、蒙特利尔认知评估量表(MoCA)、社会功能缺陷筛选量表(SDSS)评估疗效.使用R软件,采用LASSO回归分析检验PANSS评分与术后12个月MOAS评分的相关性.结果 术后3、12个月,MOAS评分、PANSS评分、SDSS评分均显著改善(P<0.05),而MoCA评分无明显变化(P>0.05).手术相关并发症大多在术后2周恢复,2例术后1年表现轻度行为懒散、兴趣缺乏的症状.术后12个月MOAS评分改善率与PANSS阳性评分改善率、术前PANSS子项被害评分呈明显正相关(P<0.05),而与PANSS子项交谈缺乏自发性和流畅性评分、不合作评分以及年龄呈明显负相关(P<0.05).结论 ALIC-RSF对难治性SCZ的攻击行为有确切疗效,可明显提高病人的社会功能和生活质量.
Somatic symptom disorder (SSD) is a form of mental illness that causes one or more distressing somatic symptoms leading to a significant disruption to everyday life, characterized by excessive thoughts, feelings, or behaviors related to these symptoms. While SSD is characterized by significant discomfort in some parts of the body, these symptoms are not related to any known medical condition and therefore it cannot be diagnosed using any medical instrument examination. Currently available treatments for SSD, including drug therapy and psychotherapy (such as cognitive behavioral therapy), usually improve psychiatric symptoms, but the results are often disappointing. Furthermore, SSD is often comorbid with anxiety and depression (75.1 and 65.7%, respectively). Importantly, interventions targeting the anterior limb of the internal capsule (ALIC; e.g., deep brain stimulation and thermal ablation) can effectively treat various mental disorders, such as refractory obsessive-compulsive disorder, depression, and eating disorders, suggesting that it may also be effective for treating the depressive symptoms associated with SSD comorbidity. In this report, a 65-year-old woman diagnosed with SSD accompanied with depression and anxiety underwent bilateral anterior capsulotomy. The patient complained of nausea and vomiting, swelling of the hilum of the liver for 14 years, weakness of the limbs for 13 years, and burning pain in the esophagus for 1 year. Psychiatric and neuropsychological assessments were conducted to record the severity of the patients' symptoms and the progression of postoperative symptoms. The patient's somatization, depression, and anxiety symptoms as well as quality of life improved significantly and steadily; thus, anti-depressive and anti-anxiety medication were stopped. However, the patient developed new somatization symptoms, including dizziness, headache, and sternal pain, 10 months after the operation. Therefore, the patient resumed taking flupentixol and melitracen in order to control the new symptoms. This study shows that bilateral anterior capsulotomy appears to be a complementary treatment for refractory SSD with depressive and anxiety symptoms. Furthermore, postoperative use of anxiolytic and antidepressant medications may be useful for controlling future somatization symptoms.
A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington's Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.
目的 探讨经Dolenc入路手术治疗海绵窦肿瘤的疗效.方法 回顾性分析2013年1月到2020年6月经Dolenc入路手术切除的60例海绵窦肿瘤的临床资料.结果 肿瘤全切除36例,次全切除9例,大部分切除15例.术后病理显示55例(91.7%)为良性肿瘤,其中脑膜瘤27例,神经鞘瘤12例,垂体腺瘤12例.术后随访半年,颅神经损伤好转率为52.9%(27/51),术后头疼缓解率为85.7%(6/7),面部麻木好转率仅为33.3%(6/18).术后新发神经受损症状40例,其中眼神经麻痹22例(56%,22/40),随访6个月好转16例(72.7%,16/22).术后视力、视野好转率为50%(7/14);新发视力受损2例,随访6个月无明显改善.多因素logistic回归分析显示肿瘤包绕颈内动脉是肿瘤未全切除的独立危险因素(P<0.05).结论 海绵窦肿瘤多数为良性肿瘤,Dolenc入路手术切除肿瘤效果良好,但颈内动脉被肿瘤包绕不利于全切除肿瘤.
Objective: To explore the clinical application of lumbar cerebrospinal fluid drainage (LCFD) during the perioperative period in the department of neurosurgery.Methods: We retrospectively analyzed the clinical data of 59 patients undergone LCFD during the perioperative period and summarize the indication and clinical experience.Results: LCFD could anticipate the effect of ventriculoperitoneal shunt before surgery, decrease intracranial pressure in surgery, which showed good curative effect in the aneurysmal subarachnoid hemorrhage, postoperative cerebrospinal fluid leakage, postoperative in-tracranial infection and subdural collection of fluid after craniotomy. No pneumocephalus, intracranial hemorrhage or intracranial infection occured. Paradoxical herniation was provoked in one patient with craniectomy and then recovered after treatment.Conclusion: The application of LCFD during the peri-operative period in the department of neurosurgery is effective and safe.
Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have previously demonstrated that glycine, a non-essential amino acid is involved in neuroprotection following intracerebral hemorrhage via the Phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway. However, whether it has a role in inducing neuroprotection in SAH is not known. The present study was designed to investigate the role of glycine in SAH. In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glycine treatment also suppressed SAH-induced M1 microglial polarization and thereby inflammation. Taken together, we conclude that glycine has neuroprotective effects in SAH and is mediated by the miRNA-26b/PTEN/AKT signaling pathway, which may be a therapeutic target for treatment of SAH injury.
Cerebral aneurysms (CAs) have become a health burden not only because their rupture is life threatening, but for a series of devastating complications left in survivors. It is well accepted that sustained chronic inflammation plays a crucial role in the pathology of cerebral aneurysms. In particular, macrophages have been identified as critical effector cells orchestrating inflammation in CAs. In recent years, dysregulated M1/M2 polarization has been proposed to participate in the progression of CAs. Although the pathological mechanisms of M1/M2 imbalance in CAs remain largely unknown, recent advances have been made in the understanding of the molecular basis and other immune cells involving in this sophisticated network. We provide a concise overview of the mechanisms associated with macrophage plasticity and the emerging molecular targets.
Objective To explore the preoperative evaluation of primary trigeminal neuralgia (TN) using 3T three-dimensional time-of-flight magnetic resonance angiography (3 D-TOF-MRA) and three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA).Methods 3D-TOF-MRA and 3D-FIESTA were performed on 52 patients with primary TN in our study.The relationship between vessels and trigeminal was compared on the symptomatic side and the asymptomatic side.The preoperative magnetic resonance imaging (MRI) findings and the surgical findings were compared.The sensitivity and specificity of preoperative MRI diagnosis were caculated.A 2-year follow-up was carried out after surgery and the relationship of preoperative MRI findings and clinical outcome was analyzed.Results The preoperative 3T MRI showed that the positive rate on the symptomatic side was 90.4%,and that on the asymptomatic side was just 25.0%.The sensitivity of preoperative MRI diagnosis was 89.8% and the specificity was 100.0%.The preoperative MRI findings were in good accordance with the surgical findings.The patients with MRI positive findings had better outcome than the patients with MRI negative findings.Conclusion Preoperative 3T MRI combined with 3D-TOF-MRA and 3D-FIESTA has good sensitivity,specificity and predictive value in primary TN patients who are candidates for microvascular decompression.
Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R injury is not yet clear. Recent studies have demonstrated that TLR4/NF- κ B signaling pathway takes part in the damaging inflammatory process of cerebral I/R injury. The present study aimed to investigate the effect of DAP on cerebral I/R injury in vivo and its possible mechanisms. DAP was administered before middle cerebral artery occlusion and reperfusion in mice. The neurological scores, cerebral infarct sizes, the levels of inflammatory cytokines, apoptotic neural cells, and the levels of TLR4, NF- κ B p65, and I κ B α were estimated. The results showed that an obvious improvement of neurological scores and infarct sizes was observed in DAP-treated mice after MCAO/R. DAP treatment decreased the overexpression of TNF- α , IL-1 β , and IL-6 and attenuated neural cells apoptosis. Moreover, DAP treatment decreased the TLR4 expression, I κ B- α degradation, and nuclear translocation of NF- κ B. Taken together, our results suggested that DAP exerted neuroprotective and anti-inflammatory effects on cerebral I/R injury. The potential mechanism was involved in the inhibition of TLR4/NF- κ B mediated inflammatory signaling pathway.
Objective To systematically assess the association between X-ray repair cross complementing 1 (XRCC1) polymorphisms and glioma risk.Methods The databases including EMbase,PubMed,Cochrane,Library,CNKI,VIP,CBMdisc were searched to collect case-control studies about genetic polymorphisms of glioma.The data were extracted and the Meta-analysis was conducted by Stata 12.0 software.Results A total of 9 studies were included in the meta-analysis,including 3788 glioma patients and 4026 controls.The overall data showed that XRCC1 Arg194Trp [allele C vs.T:odd ratio (OR) =0.83,95% confidence interval (CI):0.77-0.90;co-dominant model CC vs.TT:OR =0.59,95% CI:0.48-0.72;dominant model CC vs.CT + TT:OR =0.86,95% CI:0.79-0.95;recessive model CC + CT vs.TT:OR =0.61,95% CI:0.50-0.74] and Arg399Gln polymorphisms (allele G vs.A:OR=0.78,95% CI:0.72-0.84;co-dominant model GG vs.AA:OR=0.56,95% CI:0.47-0.66;dominant model GG vs.GA + AA:OR =0.77,95 % CI:0.70-0.84;recessive model GG + GA vs.AA:OR =0.62,95% CI:0.53-0.73) were significantly associated with glioma.However,XRCC1 Arg280His was not associated with glioma (allele G vs.A:OR =0.96,95% CI:0.75-1.23;co-dominant model GG vs.AA:OR =1.04,95% CI:0.60-1.78;dominant model GG vs.GA + AA:OR =0.96,95 % CI:0.76-1.22;recessive model GG + GA vs.AA:OR =1.03,95 % CI:0.62-1.72).Conclusion XRCC1 Arg194Trp (base C changed to T) and Arg399Gln (base G changed to A) polymorphisms increased glioma risk,and XRCC1 Arg280His (base G changed to A) was irrelevant to the increased or decreased glioma risk.
OBJECTIVES:Glioma is the most common central nervous system tumor. This systematic review and meta-analysis is aimed to systematically assess the association of XRCC1 polymorphisms with the risk of glioma.METHODS:Such databases as EMbase, PubMed, The Cochrane Library, the China National Knowledge Infrastructure (CNKI) platforms, VIP and WanFang were searched up to April 2015 to collect case-control studies of association between XRCC1 polymorphisms and glioma. Data were extracted and meta-analysis was conducted by using Stata 12.0 softwares.RESULTS:A total of 22 studies were included in the meta-analysis, including 18503 glioma patients and 24367 controls. The overall data indicated that XRCC1 Arg194Trp (C>T) polymorphism significantly increased glioma risk (allele C versus T: OR=0.72, 95% CI=0.55-0.93, CC versus TT: OR=0.55, 95% CI=0.46-0.67; CC versus CT+TT: OR=0.64, 95% CI=0.45-0.91 and CC+CT vs. TT: OR=0.61, 95% CI=0.51-0.74), especially in Asia ethnicity. XRCC1 Arg280His (G>A) polymorphism has no association with glioma (allele G versus A: OR=1.01, 95% CI=0.83-1.22; GG versus AA: OR=1.07, 95% CI=0.66-1.75; GA versus AA: OR=1.01, 95% CI=0.77-1.32; GG versus GA+AA: OR=1.01, 95% CI=0.84-1.22 and GG+GT versus AA: OR=1.06, 95% CI=0.67-1.69). XRCC1 Arg399Gln (G>A) polymorphism will significantly increase glioma risk in Asian (allele G versus A: OR=0.78, 95% CI= 0.72-0.84; GG versus AA: OR=0.56, 95% CI=0.47-0.66; GA versus AA OR=0.71, 95% CI=0.59-0.84; GG versus GA+AA: OR=0.76, 95% CI=0.68-0.84 and GG+GA vs. AA: OR=0.62, 95% CI=0.53-0.73) but not Caucasian ethnicity. XRCC1 Pro161Leu (C>T), Leu387Leu (G>A), Pro602Thr (C>A), Ser593Arg (C>G) and Glu491Lys (G>A) polymorphisms increased glioma risk in different degrees.CONCLUSION:This meta-analysis suggested that XRCC1 Arg194Trp and XRCC1 Arg399Gln (G>A) polymorphisms led to susceptibility to glioma in Asian but not Caucasian population. XRCC1 Glu491Lys (G>A), Pro161Leu (C>T), Leu387Leu (G>A), Pro602Thr (C>A), Thr304Ala (A>G) and Ser593Arg (C>G) polymorphisms will increase glioma risk. However, XRCC1 Arg280His (G>A) is irrelevant to the increased or decreased glioma risk.
Puerarin has been widely used in clinical treatment and experiment research and is considered to exert an anticancer effect recently. The present study investigated the anticancer activity of puerarin in U251 and U87 human glioblastoma cells. The cells were treated with puerarin at various concentrations for different times. Cell viability and cell proliferation were detected by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining respectively. Cell cycle and apoptosis were measured separately with PI staining and Annexin V-FITC/PI double staining method by flow cytometry. DNA damage of glioblastoma cells caused by puerarin exposure was evaluated by γ-H2AX foci detection, and the expressions of p-AKT, caspase-3 and apoptosis-related proteins were detected by Western blotting after puerarin treatment. Cell viability and proliferation of glioblastoma cells treated with puerarin were significantly lower than that of the control group; the apoptosis rate increased obviously compared to the control group. Puerarin significantly decreased the proportion at G1 phase of cell cycling accompanied by increased populations at the S and G2/M phases in both cell lines. At the same time, DNA damage level of puerarin treated cells was significantly higher than that in the control cells. Moreover, puerarin treatment suppressed the expression of p-Akt and Bcl-2 and promoted the expression of Bax and cleaved caspase-3 in U251 cells. These findings indicate that puerarin exerts antitumor effects both in U251 and U87 cells.
>在寻找哺乳动物表皮生长因子受体(epidermal growth factor receptor,EGFR)负调控蛋白的过程中,与果蝇Kek1蛋白(EGFR负反馈因子)结构相似的多亮氨酸重复区免疫球蛋白样蛋白1(1eucine-rich repeats and immunoglobulin-1ike domains 1,LRIGl)步入了研究者的视野 [1] 。2001年,Ni1sson等 [2] 从人脑中成功克隆了LRIG1基因。随后的功能研究表明LRIG1可以促进EGFR泛素化并降解,从而抑制其信号转导 [3-4] 。研究发现LRIG1在肺癌、Her2(+)乳腺癌、肾透明细胞
胶质瘤是最常见的原发性中枢神经系统脑肿瘤,起源于神经胶质,约占成人恶性中枢神经系统肿瘤的80%。其具有局部高侵袭力、高核分裂活性、血管生成和局部坏死等特点。胶质母细胞瘤(GBM,WHO Ⅳ级)是恶性程度最高的胶质瘤,其中位生存期仅14.6个月,5年生存率仅为9.8%。胶质瘤较少会转移到中枢神经系统之外,但在脑实质中有较高的侵袭性。而且,无论何种级别的胶质瘤均表现出较高的侵袭性,提示在胶质瘤发生的早期即存在这种恶性表现[1]。到目前为止,仍无针对胶质瘤有效的治疗方法,胶质瘤患者的预后亦无明显改善,且经放、化疗后肿瘤复发较明显。而且,放化疗等临床治疗手段会促进胶质瘤的侵袭能力[2]。所以,掌握胶质瘤发生发展中侵袭的分子机制可能为胶质瘤患者提供新的临床治疗方案。