Investigation on the Effectiveness of Augmented Reality Memory Training Game for Chinese Older Adults: A Randomized Controlled Trial.

Objective: To evaluate the effectiveness of augmented reality (AR) game based on n-back training paradigm as a training tool for working memory (WM) of Chinese healthy older adults. Materials and Methods: One hundred eighteen older adults self-assessed as healthy were included in this study. Individuals were randomly divided into an intervention group (n = 57) and a control group (n = 61). Interventions, consisting of a 30-minute AR game-based training and a 30-minute health science program, were administered three times per week for 4 weeks, whereas the control group was required to view a 60-minute health science program three times per week for 4 weeks. Tests, Digit Span, Corsi Block-Tapping Task (CBT), and Stroop Color and Word Test (SCWT), were conducted for all participants before and after the experiment, and the game accuracy rate of the intervention group before and after intervention was recorded. Results: There was a statistically significant difference in terms of both CBT indicators, CBT forward span (z = -2.835, P = 0.005) and CBT backward span (z = 3.285, P = 0.001), and the SCWT indicator of Stroop Words Test (SW) (z = -1.894, P = 0.048) in the two groups. The intervention group showed significant improvements in the game accuracy of both medium level (z = -3.535, P < 0.05) and of high level (z = -3.953, P < 0.05). In addition, differences were observed in subgroup analysis in the accuracy of medium level (H = 6.218, P < 0.05) and high level (H = 8.002, P < 0.05) among older people with different levels of education. Conclusion: AR game based on n-back training paradigm could improve WM of Chinese older adults, showing potential for wider promotion and adoption.

[Gene therapy strategies and prospects for neurofibromatosis type 1].

Objective: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. Methods: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. Results: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. Conclusion: Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.

Genotype-phenotype correlations of neurofibromatosis type 1: a cross-sectional study from a large Chinese cohort.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a highly heterogeneous autosomal genetic disorder characterized by a broad spectrum of clinical and molecular manifestations. The correlations between genotype and phenotype in NF1 remain elusive. This study aimed to elucidate genotype-phenotype associations in a large Chinese cohort of NF1 patients. METHODS: We included NF1 patients from our center who underwent genetic testing for NF1 variants and systemic examination. Genotype-phenotype correlation analyses were performed, focusing on variation types and involved neurofibromin domains. RESULTS: A total of 195 patients were enrolled, comprising 105 males and 90 females, with a median age of 18 years. Truncating variants, single amino acid variations, and splicing variants accounted for 139/195 (71.3%), 23/195 (11.8%), and 33/195 (16.9%), respectively. Patients with splicing variants exhibited a significantly higher prevalence of spinal plexiform neurofibromas (spinal PNF) than those with truncating variants (76.4% vs. 51.8%; p = 0.022). Variations affecting the PKC domain were associated with higher rates of cutaneous neurofibromas (CNF) (100% vs. 64.9%, p < 0.001), Lisch nodules (100% vs. 61.2%, p < 0.001), plexiform neurofibromas (PNF) (100% vs. 95.7%, p = 0.009), and psychiatric disorders (11.8% vs. 1.6%, p = 0.042). Patients with mutations in the CSRD had an elevated risk of secondary primary malignancies (11.6% vs. 2.8%, p = 0.015). GRD involvement might enhance the risk of Lisch nodules (76.9% vs. 53.7%, p = 0.044). Variations in the Sec14-PH domain were correlated with a higher rate of CNF (76.8% vs. 58.6%, p = 0.014). Additionally, we found that the p.R1748* variants carry a high risk of malignancy. CONCLUSION: Our study suggested some novel genotype-phenotype correlations within a Chinese cohort, providing innovative insights into this complex field that may contribute to genetic counseling, risk stratification, and clinical management for the NF1 population.

Knockdown of NCOR2 Inhibits Cell Proliferation via BDNF/TrkB/ERK in NF1-Derived MPNSTs.

(1) Background: malignant peripheral nerve sheath tumours (MPNSTs) are aggressive Schwann cell-derived sarcomas with dismal prognoses. Previous studies have shown that nuclear receptor corepressor 2 (NCOR2) plays a vital role in neurodevelopment and in various tumours. However, the impact of NCOR2 on the progression of MPNST remains unclear. (2) Methods: by GEO database, MPNST tissue microarray, and NF1-related tumour tissues and cell lines were used to explore NCOR2 expression level in the MPNSTs. The role and mechanism of NCOR2 in NF1-derived MPNSTs were explored by experiments in vivo and in vitro and by transcriptome high-throughput sequencing. (3) Results: NCOR2 expression is significantly elevated in NF1-derived MPNSTs and is associated with patient 10-year survival time. Knockdown of NCOR2 suppressed NF1-derived MPNST cell proliferation by blocking the cell cycle in the G0/G1 phase. Moreover, decreased NCOR2 expression could down-regulate MAPK signal activity through the BDNF/TrkB pathway. (4) Conclusions: our findings demonstrated that NCOR2 expression is significantly elevated in NF1-derived MPNSTs. NCOR2 knockdown can inhibit NF1-derived MPNST cell proliferation by weakened BDNF/TrkB/ERK signalling. Targeting NF1-derived MPNSTs with TrkB inhibitors, or in combination with ERK inhibitors, may be a novel therapeutic strategy for clinical trials.

[Treatment and progress of cutaneous neurofibroma].

Objective: To summarize current widely-used therapies for cutaneous neurofibroma (cNF) and related research progress. Methods: Based on extensive investigation of domestic and foreign research, the existing treatment of cNF, including the indications, effectiveness and trials of targeted drugs were reviewed. Results: cNF is a hallmark feature of neurofibromatosis type 1 and has a dramatic negative impact on patient appearance and quality of life. At present, there is no standard management of cNF. Invasive treatment is a commonly-used treatment. Surgical removal gives excellent cosmetic results, but it is difficult for multiple tumors; CO2 laser ablation, laser photocoagulation, electro-drying, and radiofrequency ablation are effective in treating lots of cNF at one time. Although fast and effective, these therapies can lead to depigmentation, hyperpigmentation, or extensive scarring. There is no targeted drug approval for cNF, and a series of studies have been carried out on the Ras-MEK pathway, Ras-mTOR pathway, receptor tyrosine kinase, et al. Conclusion: The treatment of cNF has developed rapidly in recent years and has broad prospects, but the individualization and precision of the treatment still needs further clinical research.

Efficacy and Safety of Trametinib in Neurofibromatosis Type 1-Associated Plexiform Neurofibroma and Low-Grade Glioma: A Systematic Review and Meta-Analysis.

Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest studies has been published. We conducted this meta-analysis to evaluate the effectiveness and safety of trametinib in treating NF1-related nerve tumors. Original articles reporting the efficacy and safety of trametinib in NF1 patents were identified in PubMed, EMBASE, and Web of Science up to 1 June 2022. Using R software and the 'meta' package, the objective response rates (ORRs) and disease control rates (DCRs) were calculated to evaluate the efficacy, and the pooled proportion of adverse events (AEs) was calculated. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Eight studies involving 92 patients were included, which had a very low to moderate quality of evidence. The pooled ORR was 45.3% (95% CI: 28.9-62.1%, I2 = 0%), and the DCR was 99.8% (95% CI: 95.5-100%, I2 = 0%). The most common AEs was paronychia, with a pooled rate of 60.7% (95% CI: 48.8-72.7%, I2 = 0%). Our results indicate the satisfactory ability to stabilize tumor progression but a more limited ability to shrink tumors of trametinib in NF1-related nerve tumors. The safety profile of trametinib is satisfactory.