Abducens schwannoma is relatively very rare, and accounts for only about 1% of all intracranial schwannomas. Here, we report microsurgical resection of a rare case of cisternal-segment abducens schwannoma in a female patient. Upon physical examination, the patient showed no eye movement symptoms, and facial & auditory nerves function were normal, but showed slight unsteady walking and positive Romberg sign. Magnetic resonance imaging (MRI) scan of the brain revealed a mass located at the right cerebellopontine angle (CPA), and the tumor was partially enhanced after contrast MRI scan. Thus, schwannoma is suspected before surgery, but it's difficult to identify its origin by MRI images. Considering tumor compression to brain stem and available microsurgical techniques nowadays, we selected craniotomy surgery for the patient, and classic retro-sigmoid approach was recommended, which is a safe and commonly used surgical approach. During the surgery, the tumor was found to arise from the abducens nerve, and a total resection of the schwannoma was finally achieved under intra-operative neuro-monitoring. The patient tolerated the surgery very well, but had transient abducens paralysis and ataxia after surgery, and gradually improved in 3 months. The follow-up brain MRI images 3 months after surgery indicated no residual or relapse of the tumor.

Vestibular schwannoma (VS), characterized by the absence of merlin expression, is the most prevalent benign tumor located at the cerebellopontine angle, lacking approved pharmaceutical interventions except for off-label utilization of bevacizumab. The role of Tumor stiffness-Focal adhesion kinase (FAK) activation in fueling tumor progression is well-established, with merlin deficiency serving as a biomarker for tumor sensitivity to FAK inhibitors. In this context, we investigated whether Tumor stiffness-FAK contributes to VS progression. Single-cell RNA sequencing revealed associations between VS progression and gene sets related to “Response to mechanical stimulus” and “Neurotrophin signaling pathway”. Histological studies indicated a potential involvement of neurotrophins in early stages of VS tumorigenesis, while enhanced Extracellular matrix (ECM) remodeling-Tumor stiffness-FAK signaling accompanies later stages of VS progression. In vitro experiments demonstrated that elevated matrix stiffness induces cytoskeletal remodeling, cell proliferation, and metalloproteinase expression in VS cells by activating FAK. Conversely, FAK inhibition diminishes these effects. Collectively, this study suggests that ECM remodeling-Tumor stiffness contributes to VS progression via FAK activation, positioning FAK as a promising therapeutic target in treating VS.

INTRODUCTION:Neurofibromatosis type 2 (Nf2) gene inactivation is common in sporadic and Nf2-related meningioma. There is currently scant literature describing the development of an intracranial meningioma model in animals. Given the role of Nf2 and other gene inactivation in meningeal cells, we used Cas9 mice here as the background host to establish a new animal model of skull base meningioma in this study. AIMS:Cas9 transgenic mice were purchased from Jackson Laboratory and raised in our institution. Subsequently, meningeal cells were obtained from the Cas9 transgenic mice, cultured in medium, and passaged in vitro. We then prepared lentivirus vector pLentiCre/gRNA, which could express the elements blocking the function of four genes: Nf2, P15Ink4b, P16Ink4a, and P19Arf. We infected the meningeal cells with the lentivirus vector pLentiCre/gRNA and tested the expression of these four genes in those infected meningeal cells. Next, adeno-associated virus vector pAAVCre/gRNA was injected in vivo into the skull base meningeal cells of the neonate Cas9 transgenic mice. These mice were observed once a week and killed 10 months later for brain inspection and pathological analysis. RESULTS:Twenty Cas9 transgenic mice were successfully bred. Five mice were killed so that meningeal cells could be extracted, cultured, and infected with the lentivirus vector pLentiCre/gRNA for 72 h in vitro. The gene function test showed that Nf2, P15Ink4b, P16Ink4a, and P19Arf were all blocked in the infected meningeal cells, which indicated that the lentivirus vector pLentiCre/gRNA could effectively block the expression of the four genes in targeted cells. Then pAAVCre/gRNA was injected into the skull base meningeal cells of 15 mice in vivo, and nine mice were observed for 10 months so that the intracranial tumor growth could be assessed. Among these nine mice, pathological analysis showed that six mice had benign meningioma subtypes similar to human meningioma, one mouse had atypical meningioma, one mouse had malignant meningioma, and one mouse had sarcoma. CONCLUSIONS:The Cas9 mouse model of skull base meningioma generated with the Nf2 genetic defect and the combinational loss of P15Ink4b, P16Ink4a, and P19Arf could provide a new tool for investigating the pathogenesis of meningioma and the development of chemical interventions for this disease.

Background:Angioleiomyoma is a benign lesion of mesenchymal origin, which always occurs in the uterine system. Pathologically, angioleiomyoma is usually composed of well-differentiated smooth muscle cells with few mitotic features. However, primary intracranial angioleiomyoma represents an exceedingly rare tumor, since the first case reported in 1994. Case Description:Here, we reported a case of primary intracranial angioleiomyoma, which mimicking meningioma in pre-operative images. The patient was a 42-year-old male, presented with dizziness and unsteady walking for about 6 months, without symptoms of cranial nerve deficit. Head computer tomography scan showed a well-defined lesion adjacent to right brain stem with high intensity. Contrast brain magnetic resonance imaging (MRI) scan exhibited an extra-axial mass with homogeneous enhancement located at the right pontine, presented as meningioma features; however, other tumors including lymphoma should be differentiated as well. The patient underwent sub-temporal craniotomy for the tumor resection. Histological analysis confirmed the diagnosis of angioleiomyoma. Follow-up brain MRI scan (6 months after surgery) showed total resection of the lesion without residual. Conclusions:In summary, primary intracranial angioleiomyoma is rare. Thus, diagnosis and differential diagnosis are important before surgical resection, which was mimicking meningioma in our case. Pathological analysis could reveal spindle shaped cells with few mitotic features, and confirm the diagnosis of angioleiomyoma. Currently, the optimal therapy for primary intracranial angioleiomyoma is surgical resection, and adjuvant radiation therapy for the residual tumor. However, long-term prognosis of the disease should be monitor in the future.

BackgroundTrichomoniasis caused by Trichomonas vaginalis, combined with its complications, has long frequently damaged millions of human health. Metronidazole (MTZ) is the first choice for therapy. Therefore, a better understanding of its trichomonacidal process to ultimately reveal the global mechanism of action is indispensable. To take a step toward this goal, electron microscopy and RNA sequencing were performed to fully reveal the early changes in T. vaginalis at the cellular and transcriptome levels after treatment with MTZ in vitro.ResultsThe results showed that the morphology and subcellular structures of T. vaginalis underwent prominent alterations, characterized by a rough surface with bubbly protrusions, broken holes and deformed nuclei with decreased nuclear membranes, chromatin and organelles. The RNA-seq data revealed a total of 10,937 differentially expressed genes (DEGs), consisting of 4,978 upregulated and 5,959 downregulated genes. Most DEGs for the known MTZ activators, such as pyruvate:ferredoxin oxidoreductase (PFOR) and iron-sulfur binding domain, were significantly downregulated. However, genes for other possible alternative MTZ activators such as thioredoxin reductase, nitroreductase family proteins and flavodoxin-like fold family proteins, were dramatically stimulated. GO and KEGG analyses revealed that genes for basic vital activities, proteostasis, replication and repair were stimulated under MTZ stress, but those for DNA synthesis, more complicated life activities such as the cell cycle, motility, signaling and even virulence were significantly inhibited in T. vaginalis. Meanwhile, increased single nucleotide polymorphism (SNP) and insertions - deletions (indels) were stimulated by MTZ.ConclusionsThe current study reveals evident nuclear and cytomembrane damage and multiple variations in T. vaginalis at the transcriptional level. These data will offer a meaningful foundation for a deeper understanding of the MTZ trichomonacidal process and the transcriptional response of T. vaginalis to MTZ-induced stress or even cell death.

目的 总结幕下开颅肿瘤手术并发的远隔部位血肿病例,探讨早期识别方法和防治策略.方法 回顾性分析复旦大学附属华山医院神经外科颅底亚专科组自2019年12月至2021年11月收治的幕下开颅肿瘤手术患者的临床资料,总结远隔部位血肿发生部位、血肿类型,分析产生原因,探讨术中术后如何早期识别及防治策略.结果 490例幕下开颅肿瘤手术患者中,出现远隔部位血肿18例(3.67%),其中幕上硬膜下血肿9例,枕部硬膜外血肿3例,幕上硬膜下血肿合并纵裂血肿2例,脑室内血肿2例,纵裂血肿1例,颞叶脑内血肿合并蛛网膜下腔出血1例.2例患者术中准确识别,终止手术,术中CT复查明确出血类型后手术治疗;16例在术后早期识别,CT复查明确出血类型,1例采取手术治疗,15例采取保守治疗.所有18例病例术后随访2～21个月,无死亡病例.结论 幕下开颅肿瘤手术并发远隔部位血肿是一种少见且严重威胁手术安全的并发症,多表现为幕上硬膜下血肿、硬膜外血肿、脑室内血肿及脑内血肿等,可合并蛛网膜下腔出血;围手术期积极预防、早期准确识别和及时有效的处理能显著改善患者的预后.

Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA. All data were downloaded from the public database. Limma package and ssGSEA algorithm was used to identify differentially expressed mRNAs (DEmRNAs) and analyze immune cell infiltration, respectively. Machine learning and cytoscape-cytohubba plug-in was used to identify key immune types and multicentric DEmRNAs of IA, respectively. Multicentric DEmRNAs related to key immune cells were screened out as key DEmRNAs by Spearman correlation analysis. Diagnostic models, competing endogenous RNA (ceRNA) regulatory network and transcription factor regulatory network were constructed based on key DEmRNAs. Meanwhile, drugs related to key DEmRNAs were screened out based on DGIdb database. The expression of key DEmRNAs was also verified by real time-PCR. In this study, 7 key DEmRNAs (NRXN1, GRIA2, SLC1A2, SLC17A7, IL6, VEGFA and SYP) associated with key differential immune cell infiltration (CD56bright natural killer cell, Immature B cell and Type 1 T helper cell) were identified. Functional enrichment analysis showed that VEGFA and IL6 may be involved in the regulation of the PI3K-Akt signaling pathway. Moreover, IL6 was also found to be enriched in cytokine-cytokine receptor interaction signaling pathway. In the ceRNA regulatory network, a large number of miRNAs and lncRNAs were found. In the transcription factor regulatory network, the transcription factor SP1 was correlated with VEGFA, SYP and IL6. It is also predicted that drugs related to key DEmRNAs such as CARBOPLATIN, FENTANYL and CILOSTAZOL may contribute to the treatment of IA. In addition, it was also found that SVM and RF models based on key DEmRNAs may be potential markers for diagnosing IA and unruptured intracranial aneurysm (UIA), respectively. The expression trend of key DEmRNAs verified by real-time PCR was consistent with the bioinformatics analysis results. The identification of molecules and pathways in this study provides a theoretical basis for understanding the immune related molecular mechanism of IA. Meanwhile, the drug prediction and diagnosis model construction may also be helpful for clinical diagnosis and management.

Abstract Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. Registration: Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234

Vestibular schwannoma (VS) is one of the most common types of benign tumors of the central nervous system. At present, the prevailing treatment methods of VS include surgery, stereotactic radiotherapy, and follow-up observation, etc. However, there is still no drug therapy available for treating VS. Although the surgical technique is relatively mature, the complications cannot be completely avoided. Furthermore, both the growth rate of different cases and patients' sensitivity to radiotherapy vary greatly. With the constant progress made in molecular biology research, most of the studies on the growth mechanism of VS focus on the upstream and downstream of neurofibromin 2 ( NF2) gene and merlin protein, and a number of corresponding targets, including receptor protein tyrosine kinase (RTK), vascular endothelial growth factor receptor (VEGFR), mammalian target of rapamycin complex 1 (mTORC1) and platelet derived growth factor receptor (PDGFR). It has been reported in some studies that quite a few drugs could inhibit the proliferation of VS cells. Most of the studies are still in the stage of in vitro cell experiment and/or animal experiment. A small number of studies have entered phase Ⅰ and phase Ⅱ clinical trials, but have not led to any clinical treatment yet. This paper provides a comprehensive understanding of the current status and the prospects of drug therapies of VS, which is conducive to the development of subsequent research.

Background: Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. Methods: Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. Results: In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was >0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. Conclusion: Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.

Previous studies have demonstrated that inversion effect and left-side bias are stable expertise markers in Chinese character processing among adults. However, it is less clear how these markers develop early on (i.e., among primary school students). Therefore, this study aimed to investigate the development of the two markers by comparing primary school-aged students of three age groups (Grade 1, Grade 3, and Grade 5) and adults in tests of inversion effect (Experiment 1) and left-sided bias effect (Experiment 2). The results replicated that both effects during Chinese character processing were present among adults. However, more importantly, the effects were different among primary school-aged students in different grades: the inversion effect was found as early as in Grade 1, but the left-side bias effect did not emerge in Grade 1 and as approximated that of adults until Grade 3. The study suggested a potential dissociation in developing different aspects of expertise during Chinese character processing in early childhood.

BackgroundLumboperitoneal shunt (LPS) is now an effective surgical modality for idiopathic normal pressure hydrocephalus (iNPH), but there is still a lack of clinical data on LPS in older adult iNPH patients in China. We aim to report the shunt effect and the complications of older adult iNPH patients treated with LPS at a single center in Shanghai, China.MethodsWe conducted a retrospective study among adults over 60 years old who were diagnosed as iNPH and treated with LPS from September 2016 to December 2020. The shunt effect was evaluated from two dimensions of functional and symptomatic improvement 3 months and 1 year after surgery, respectively. The potential factors related to the shunt effect one year after surgery were explored by comparing the effect between different subgroups and conducting multivariate logistic regression analysis.ResultA total of 85 patients were included in this study, ranging from 60 to 93 years old, with an average age of 74.7. The function and symptoms were better both 3 months and 1 year after surgery than before (P < 0.001). At the 1-year postoperation follow-up, the functional and symptomatic improvement rates were 72.9% and 90.6%, respectively. The symptomatic improvement rates of gait, urination, and cognition were 74.1%, 72.9%, and 60.0%, respectively. Multivariate logistic regression analysis showed that improvement in function was much more possible in patients with less than 24 months from symptom onset to surgery (OR = 24.57, P < 0.001) and those with disproportionately enlarged subarachnoid-space hydrocephalus (OR = 5.88, P = 0.048); improvement in gait was also more possible in patients with less than 24 months from symptom onset to surgery (OR = 5.29, P = 0.017); improvement in urination was more possible in patients with diabetes (OR = 4.76, P = 0.019), and improvement in cognition was more possible in patients with preoperative modified Rankin scale level lower than 4 (OR = 3.51, P = 0.040). Minor operation-related complications were seen in 27 patients (31.8%) and severe complications in 6 patients (7.1%).ConclusionLPS could improve the function and symptoms of older adult iNPH patients. Early detection, diagnosis, and treatment of the disease could improve the shunt effect of the patients. Older adult iNPH patients with higher age ranges could achieve comparable shunt results compared with younger adults.

目的 探讨总胆红素(TBil)水平与老年脑小血管病(CSVD)患者认知功能障碍的关系.方法 纳入社区老年CSVD患者277例,采用简易精神状态检查量表(MMSE)对其进行神经心理学评价,根据MMSE评分将其分为认知功能障碍组88例和认知功能正常组189例.比较两组患者的流行病学特征、TBil水平及血脂等临床资料,并采用多因素logistic回归分析评估老年CSVD患者认知功能障碍的影响因素.结果 认知功能障碍组的年龄、合并高血压和糖尿病患者比例、总胆固醇水平均明显高于认知功能正常组,受教育年限及TBil水平明显低于认知功能正常组(P<0.05).多因素logistic回归分析结果显示,年龄和总胆固醇水平较高、受教育年限较短及TBil水平降低是老年CSVD患者发生认知功能障碍的危险因素(P<0.05),其中低水平血清TBil患者发生认知功能障碍的风险是高水平血清胆红素患者的8.79倍.结论 较低水平的血清TBil与老年CSVD患者发生认知功能障碍密切相关.

Background: Subjective cognitive decline (SCD) has been called the prodromal stage of amnestic mild cognitive impairment (aMCI); however, further investigation is needed to confirm this observation. Objective: To define the relationship between SCD and aMCI. Method: In this case-control study, we used the feeling-of-knowing in episodic memory (FOK–EM) test to measure the memory-monitoring function of 40 adults with aMCI, 60 with SCD, and 55 healthy controls. Results: The recognition rates of FOK–EM (53.53% ± 7.82%; 55.12% ± 6.08%) and judgment accuracy of the aMCI and SCD groups (γ values 0.21 ± 0.11; 0.30 ± 0.16) were significantly lower than those of the control group (72.32% ± 5.14%; 0.57 ± 0.16) (F = 116.24, P < 0.01; F = 128.57, P < 0.01; F = 73.33, P < 0.01). The scores for correct decision/correct recognition (RR; 27.2 ± 6.43; 29.36 ± 5.16) and correct decision/false recognition (RF; 30.41 ± 5.06; 27.26 ± 4.37) of the aMCI and SCD groups were also significantly lower than those of the control group (49.35 ± 7.13; 11.16 ± 4.35) (F RR = 132.67, P < 0.01; F RF = 131.8, P < 0.01). Conclusion: Mild clinical impairments in memory-monitoring function may precede clinically confirmed objective memory impairment in individuals with SCD.

Literacy acquisition can modulate the way we process visual words and language. However, little is known about its function in reshaping how we process non-linguistic materials, like faces. In this study, we explored this question by comparing the facial recognition skills of illiterate and literate adults in China. Our results showed that illiterates were less sensitive to changes in spatial configuration among key features in upright faces when stimuli were presented simultaneously. The differences in sensitivity of spatial configuration between the literates and illiterates were also observed in house processing. These results thus provide evidence that literacy acquisition during childhood could reshape configural processing.

Hyperglycemia is common in patients with acute ischemic stroke and is associated with poor outcomes.International guidelines recommend that patients with acute ischemic stroke should maintain their blood glucose level within an appropriate range using the loose treatment.However,specific hypoglycemic measures are still inconclusive.This article reviews the research progress of hyperglycemia after acute ischemic stroke.

Objective To investigate the correlation of Cysc with the severity of cerebral microbleeds and cognitive impaiment. Methods 76 cerebral microbleeds patients ( CMBs group) and 72 healthy persons ( control group) were se-lected,the cognitive function of all participants were evaluated by MoCA. According to the number of lesions of CMBs on SWI,the CMBs group was divided into 1 (1),2 (2~5) and 3 ( >5). The correlation of Cysc with the severity of cerebral microbleeds and cognitive impaiment was analyzed. Results The Cysc level of CMBs group was significantly higher than the control group,there was significant difference between the groups (P<0. 01). The MoCA score of CMBs group was sig-nificantly lower than the control group,there was significant difference between the groups (P<0. 01). With the aggravation of the severity of cerebral microhemorrhage,the level of cystatin C increased gradually,the difference was statistically signifi-cant (P<0. 01);with the aggravation of the severity of cerebral microhemorrhage,MoCA score decreased gradually,the difference was statistically significant (P<0. 01). The level of Cysc was positively correlated with cerebral microbleeds (P=0. 0002). The level of Cysc was negatively correlated with MoCA score in patients with cerebral microbleeds(P =0. 0001). Conclusion The higher the level of cystatin C,the more severe the cerebral microbleeds,the more serious cogni-tive impairment.

血红素氧合酶(heme oxygenase,HO)是血红素降解过程中的限速酶,迄今已发现 HO 有3 种亚型:HO-1、HO-2 和HO-3. HO-1能将具有氧化性质的血红素分解生成具有抗氧化性质的胆红素和抗炎症作用的CO,而发挥抗炎症与抗氧化应激等细胞保护功能[1]. 作为发病与炎症和氧化应激密切相关的缺血性脑血管病,HO-1水平与其的关系目前国内外鲜有报道. 本研究通过检测缺血性脑血管病患者及正常对照组血清HO-1 水平,为进一步探索通过调节HO-1 的表达用于临床提供理论依据.