Linc-NSC affects cell differentiation, apoptosis and proliferation in mouse neural stem cells and embryonic stem cells in vitro and in vivo.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.

Large vestibular schwannomas presenting in the late state of pregnancy: a case report and literature review.

Vestibular schwannomas in pregnancy have rarely been reported, and there is a lack of in-depth discussion on the experience of management of massive acoustic neuromas in pregnancy. Herein, we present a pregnant woman with a giant vestibular schwannoma and obstructive hydrocephalus who presented at 30 weeks of gestation. She was initially misdiagnosed as having a pregnancy-related reaction of headache, dizziness, and vomiting that had occurred 2 months earlier. After observation at home, her symptoms progressed at 30 weeks of gestation, and imaging findings revealed a brain tumor in the CPA region with secondary cerebella tonsil herniation and obstructive hydrocephalus, and she was transferred to our center for treatment. Consequently, we relieved her hydrocephalus with a ventriculoperitoneal shunt (V-P shunt) and used corticosteroids to simulate fetal maturation. After 10 days, her mental condition deteriorated, and her right limb muscle strength gradually decreased until grade 0 (MMT Grading). Finally, under a joint consultation with the Department of Neurosurgery, Obstetrics, and Anesthesiology, she underwent a cesarean section under general anesthesia and first-stage tumor removal at 31 weeks of gestation. Upon discharge, the previously observed neurological deficits, which were reversible and had manifested during her gestational period, had been successfully resolved, and the fetus had been conserved. The neuroimaging confirmed the complete tumor removal, while the neuropathologic examination revealed a vestibular schwannoma. Therefore, we recommend early diagnosis and treatment for these patients, especially people with headaches, vomiting, and sudden hearing loss during pregnancy. Herein, we concluded that our cases provide a valuable experience in the latest acceptable time frame for the operation to prevent irreversible neurological impairment and premature delivery in late pregnancy.

Research process, recap, and prediction of Chiari malformation based on bicentennial history of nomenclature and terms misuse.

There is an absent systematic analysis or review that has been conducted to clarify the topic of nomenclature history and terms misuse about Chiari malformations (CMs). We reviewed all reports on terms coined for CMs for rational use and provided their etymology and future development. All literature on the nomenclature of CMs was retrieved and extracted into core terms. Subsequently, keyword analysis, preceding and predicting (2023-2025) compound annual growth rate (CAGR) of each core term, was calculated using a mathematical formula and autoregressive integrated moving average model in Python. Totally 64,527 CM term usage was identified. Of these, 57 original terms were collected and then extracted into 24 core-terms. Seventeen terms have their own featured author keywords, while seven terms are homologous. The preceding CAGR of 24 terms showed significant growth in use for 18 terms, while 13, three, three, and five terms may show sustained growth, remain stable, decline, and rare in usage, respectively, in the future. Previously, owing to intricate nomenclature, Chiari terms were frequently misused, and numerous seemingly novel but worthless even improper terms have emerged. For a very basic neuropathological phenomenon tonsillar herniation by multiple etiology, a mechanism-based nosology seems to be more conducive to future communication than an umbrella eponym. However, a good nomenclature also should encapsulate all characteristics of this condition, but this is lacking in current CM research, as the pathophysiological mechanisms are not elucidated for the majority of CMs.

A Novel Craniocervical Junction Compression Severity Index-Based Grading System for Multidirectional Quantification of the Biomechanics at Foramen Magnum of Chiari Malformation Type I.

Objective This study aimed to establish a novel grading system, based on the craniovertebral junction compression severity index (CVJCSI) for multidirectional quantification at the foramen magnum plane for Chiari malformation type I (CMI). Methods The CVJCSI grading system was established to stratify patients based on the ventral (modified clivoaxial angle < 138°), dorsal (tonsil herniation), and central (brainstem herniation) CVJ (craniovertebral junction) compression, the CVJCSI grading system was established to stratify patients. The optimal surgical method for each grade was recommended by intragroup comparisons regarding the efficacy of the three operations. Finally, according to the CVJCSI grading system, a prospective validation trial was performed and surgically treated for internal validation. Results Based on the retrospective study ( n = 310), the CVJCSI included six grades: I: syrinx alone without compression; II: dorsal compression; III: dorsal and central compression; IV: ventral compression; V: dorsal and ventral compression; and VI: ventral, dorsal, and central compression. Among all available variables, only the CVJCSI and surgical methods significantly affected the CCOS. The CCOS scores, overall and for each CVJCSI grade, increased in the prospective cohort ( n = 42) compared with that in the retrospective analysis. Conclusions The CVJCSI can be used to stratify CMI patients. The higher the CVJCSI grade, the more severe the CVJ compression and the worse posterior fossa deformity. Meanwhile, the CVJCSI was negatively correlated with the CCOS. The lower the CVJCSI grade, the better the response to surgery, and the less-invasive surgical procedures were warranted. Finally, the prospective cohort study validated the proposed CVJCSI-based surgical protocols.

Prevalence and treatment of typical and atypical headaches in patients with Chiari I malformation: A meta-analysis and literature review.

OBJECTIVE: A meta-analysis was conducted to analyze the incidence of typical and atypical headaches and outcomes following various treatments in patients with Chiari I malformation. BACKGROUND: Headache is the most common symptom of Chiari malformation, which can be divided into typical and atypical subgroups to facilitate management. Much controversy surrounds the etiology, prevalence and optimal therapeutic approach for both types of headaches. METHOD: We identified relevant studies published before 30 July 2022, with an electronic search of numerous literature databases. The results of this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULT: A total of 1913 Chiari malformation type I CIM patients were identified, 78% of whom presented with headache, within this group cephalgia was typical in 48% and atypical in 29% of patients, and migraine was the most common type of atypical headache. The ratio of typical/atypical headaches with international classification of headache disorders diagnosis was 1.53, and without international classification of headache disorders diagnosis was 1.56, respectively. The pooled improvement rates of typical headaches following conservative treatment, extradural decompression and intradural decompression were 69%, 88%, and 92%, respectively. The corresponding improvement rates for atypical headaches were 70%, 57.47%, and 69%, respectively. The complication rate in extradural decompression group was significantly lower than in intradural decompression group (RR, 0.31; 95% CI: 0.06-1.59, I2 = 50%, P = 0.14). Low reoperation rates were observed for refractory headaches in extradural decompression and intradural decompression groups (1%). CONCLUSION: The International Classification of Headache Disorders can assist in screening atypical headaches. extradural decompression is preferred for typical headaches, while conservative therapy is optimal for atypical headaches. A definite correlation exists between atypical headaches and Chiari Malformation Type I patients with higher prevalence than in the general population. Importantly, decompression is effective in relieving headaches in this particular patient population.

Anti-contactin-associated protein-like 2 antibody autoimmune encephalitis with rapidly progressive parkinsonism: a case report and literature review.

OBJECTIVE: Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis (AE) that often presents with epilepsy, cognitive dysfunction, peripheral neuropathy, autonomic nerve damage, and ataxia. Parkinsonism is often observed in neurodegenerative diseases but progresses slowly, and rapidly progressive parkinsonism is rare. Given that it is a curable parkinsonism, identifying and providing early immunotherapy is crucial. METHODS: We reported a patient initially presenting with anxiety and depression, whose symptoms were relieved following mood regulation treatment. After discontinuation of the mood-regulating drugs, mood disorders recurred, accompanied by parkinsonism. The onset of parkinsonism was subacute (< 3-month disease course), and progression was rapid. After immunotherapy, all symptoms disappeared completely. We reviewed all relevant literature on anti-CASPR2 antibody encephalitis with parkinsonism. RESULTS: Our literature review revealed three cases (including our patient): two male and one female, ranging in age from 48 to 72 years. All patients had parkinsonism, generalized tonic-clonic seizures, and hyponatremia. Three patients had anti-CASPR2 antibody positivity in the serum, and one patient had anti-CASPR2 antibody positivity in the CSF. All three patients were treated with anti-epileptic drugs and intravenous steroid pulse therapy, followed by oral steroid therapy, symptoms improved. CONCLUSION: Parkinsonism can be easily misdiagnosed as a neurodegenerative disease, especially during the early stages. In patients with parkinsonism, treatable diseases should be considered in addition to neurodegenerative diseases. In clinical practice, anti-CASPR2 antibody encephalitis should be considered if rapidly progressing parkinsonism is encountered after ruling out common etiologies.

Machine-learning-based risk stratification for probability of dying in patients with basal ganglia hemorrhage.

To confirm whether machine learning algorithms (MLA) can achieve an effective risk stratification of dying within 7 days after basal ganglia hemorrhage (BGH). We collected patients with BGH admitted to Sichuan Provincial People's Hospital between August 2005 and August 2021. We developed standard ML-supervised models and fusion models to assess the prognostic risk of patients with BGH and compared them with the classical logistic regression model. We also use the SHAP algorithm to provide clinical interpretability. 1383 patients with BGH were included and divided into the conservative treatment group (CTG) and surgical treatment group (STG). In CTG, the Stack model has the highest sensitivity (78.5%). In STG, Weight-Stack model achieves 58.6% sensitivity and 85.1% specificity, and XGBoost achieves 61.4% sensitivity and 82.4% specificity. The SHAP algorithm shows that the predicted preferred characteristics of the CTG are consciousness, hemorrhage volume, prehospital time, break into ventricles, brain herniation, intraoperative blood loss, and hsCRP were also added to the STG. XGBoost, Stack, and Weight-Stack models combined with easily available clinical data enable risk stratification of BGH patients with high performance. These ML classifiers could assist clinicians and families to identify risk states timely when emergency admission and offer medical care and nursing information.

CAMTA1, a novel antitumor gene, regulates proliferation and the cell cycle in glioma by inhibiting AKT phosphorylation.

Identifying biomarkers for the early diagnosis of glioma and elucidating the molecular mechanisms underlying the development of this cancer are of considerable clinical importance. Recently, studies performing microarray profiling of genes to identify distinct gene signatures reported specific subtypes with predictive and prognostic relevance. Thus, we performed deep sequencing on a total of 26 glioma tissue samples to identify the frequently mutated of oncogenes and tumor suppressors in gliomas. A total of 2306 single-nucleotide polymorphisms (SNPs) and 2010 insertion and deletion sites (indels) were found by aligning sequencing information from 26 glioma samples with sequences from the normal human gene database (GRCh37/hg19). GSEA results suggest that an underexpressed gene, calmodulin binding transcription activator 1 (CAMTA1), participates in the cell proliferation and cell cycle regulation of glioma cells. Moreover, overexpression of CAMTA1 in glioma cells notably inhibited cell growth, migration, invasion and cell cycle and enhanced temozolomide (TMZ)-induced cell apoptosis in glioma cells, while CAMTA1 overexpression decreased the ITGA5, ITGB1, p-AKT, p-FAK, and Myc protein levels, suggesting that the signaling pathways of these proteins might be involved in the cellular functions of CAMTA1 in glioma. Moreover, overexpression of CAMTA1 attenuated the growth and tumorigenesis of glioma in vivo. In summary, we identified high-frequency mutant genes in glioma and provided an experimental basis for a novel mechanism by which CAMTA1 may serve as a tumor suppressor in glioma.

Significance of Modified Clivoaxial Angles in the Treatment of Adult Chiari Malformation Type I.

OBJECTIVE: To investigate the influence of modified clivoaxial angle (MCAA) on the surgical planning and outcome in adult patients with Chiari malformation type I. METHODS: Clinical data of 268 adult patients undergoing posterior fossa decompression without (PFD) or with duraplasty (PFDD) or with resection of tonsils (RT) for Chiari malformation type I over 10 years were reviewed retrospectively, with outcome evaluated by Chicago Chiari Outcome Scale (CCOS) score. By means of receiver operating characteristic curve, the threshold of MCAA was calculated to stratify the patients. RESULTS: MCAA was positively correlated with CCOS score. In the MCAA ≤ 127° group (n = 57) with severe ventral cervicomedullary compression (VCMC), CCOS score of PFD, PFDD, and RT was 11.00, 11.06, and 12.42 (P < 0.05), respectively. In the 127° < MCAA ≤ 138° group (n = 87) with moderate VCMC, CCOS score of PFD, PFDD, and RT was 11.71, 12.72, and 13.00 (P < 0.01), respectively. In the MCAA > 138° group (n = 124) with mild or no VCMC, CCOS score of PFD, PFDD, and RT was 13.19, 13.90, and 13.67 (P < 0.05), respectively. The mean MCAA increased by 4.4° postoperatively (P < 0.05), which was positively associated with syringomyelia shrinkage. CONCLUSIONS: MCAA may play a role in guiding the surgical treatment and predicting the prognosis in adult CMI patients. The larger the MCAA, the less invasive surgery is preferred with higher CCOS. PFDD should be the first choice in patients with mild or no VCMC (MCAA >138°) and RT in patients with moderate VCMC (127° < MCAA ≤ 138°). For patients with severe VCMC (MCAA ≤ 127°), RT could be considered as the primary surgery with awareness of the possible insufficiency of posterior decompression alone.