10044 Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease characterized by multiple progressive tumor and non-tumor manifestations, with abnormal activating MAPK pathway. Plexiform neurofibromas (PN) presents in 20-50% of NF1 patients (pts) and may cause serious complications. One MEK1/2 inhibitor was approved for pediatric pts with NF1-related PN in US, EU and China, but therapeutic options remain limited. Luvometinib is a highly potent selective anti-tumorigenic inhibitor of MEK1/2, potentially effective in NF1-related PN. Previous studies have confirmed that luvometinib is expected to be a targeted therapy for neurofibromatosis type 1 in pediatric patients (pts). Methods: This multi-center, open-label phase 2 clinical trial is to assess safety and efficacy of luvometinib in pediatric pts with NF1- related PN. The primary endpoint was objective response rate (ORR) evaluated by investigators (INV). The key secondary endpoint was ORR evaluated by Blinded independent review committee (BIRC), and other secondary endpoints include 1-year PFS and others. Preliminary findings from the phase 2 trial were previously disclosed at ASCO 2024. Here, we present the updated efficacy and safety results in pediatric participants. Results: As of data cut-off (September 23, 2024), 46 pediatric pts were enrolled and treated with a dose of 5 mg/m 2 (the recommended phase 2 dose according to phase 1 study). The median follow-up time was 25.1 months. ORR evaluated by INV was 60.5% (95%CI: 44.4, 75.0), and 26 pts had partial response. ORR evaluated by BIRC was 44.2% (95%CI: 29.1, 60.1), and 19 pts had partial response. 11 of 14 pts (78.6%) with tumor pain at baseline (overall tumor pain NRS≥2) decreased to 0 points. The median DOR and median PFS were still not reached. 1-year PFS rate evaluated by INV was 95.3%. 45 pts (97.8%) experienced treatment-related adverse events (TRAEs). Among these, grade ≥3 TRAEs occurred in 10 pts (21.7%), including folliculitis(4.3%), dermatitis acneiform (4.3%), blood creatine phosphokinase increased (4.3%), ejection fraction decreased (2.2%), upper respiratory tract infection (2.2%), pneumonia (2.2%), anemia (2.2%) and gastrointestinal disorders (2.2%). 2 pts (3.1%) reported treatment-related serious adverse events. 14 pts (30.4%) experienced TRAEs led dose interruption. No reported TEAE led to dose reduction, discontinuation or death. No new safety signal was observed. Conclusions: Overall, luvometinib was well-tolerated and demonstrated promising anti-tumor activity in pediatric participants with NF1-related PN. Long-term efficacy and safety follow-up are ongoing. Clinical trial information: NCT04954001 .

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by plexiform neurofibromas (PNs), which are present in 20–60

Fucoidan, a sulfated polysaccharide predominantly derived from brown algae, has garnered significant research interest due to its diverse biological activities and potential biomedical applications. This review systematically examines both established and novel extraction methods for fucoidan. Traditional techniques, including hot water, acid, and alkaline extraction, are summarized, alongside emerging approaches such as enzymatic hydrolysis, ultrasound-assisted, microwave-assisted, and subcritical water extraction, which demonstrate enhanced efficiency and yield. The paper further synthesizes the extensive research on the compound's multifaceted physiological functions, highlighting its immunomodulatory, anti-tumor, antioxidant, anticoagulant, lipid-lowering, and antiviral properties. These findings collectively underscore the critical relationship between fucoidan's structural characteristics—influenced by its monosaccharide composition, molecular weight, and sulfation pattern—and its resultant bioactivities. The conclusion affirms fucoidan's substantial value and broad applicability, particularly within the biomedical sector, for advancing health and therapeutic strategies.

3096 Background: Neurofibromatosis type 1(NF1) is an autosomal dominant tumor predisposition syndrome characterized by NF1 gene variants, resulting in over-activation of the RAS pathway. Plexiform neurofibroma (PN) is benign tumors that arise from nerve tissue and are a hallmark feature of NF1. They typically grow along nerves and cause disfigurement, pain, and other complications depending on their location and size. FCN-159, a highly potent and selective inhibitor of MEK1/2 by targeting inhibition of the RAS pathway, holds promise as a therapeutic agent for treating NF1-related PN. Methods: A multi-center, open-label phase 1/2 clinical trial was conducted to assess the safety and efficacy in pediatric patients(pts) with NF1-related PN. Here, we reported the safety and efficacy outcomes observed during phase 2 in pediatric pts, who received FCN-159 at the 5 mg/m2 dose once daily on a continuous basis in a 28-day cycle. Preliminary findings from the phase 1/2 trial were previously disclosed at ASCO 2023. Results: As of November 24, 2023,46 pts enrolled. The median age is 8.0 years (range 2-17). The most frequent PN related complications were disfigurement (69.6%) and pain (63.0%). Median volume of target neurofibroma were 37.7 cm³ (range 2.2-1144.1). Efficacy outcomes are reported for 43 pts (modified intent-to-treat population). With the median follow-up of 15.1 months (range 14.1-16.4), the investigator and Blinded Independent Review Committee (BIRC) assessed ORR were 48.8% and 30.2%, respectively. The mDoR and median mPFS were not reached. Preliminary efficacy data are presented in the table. Among the 16 pediatric subjects with tumor pain at baseline (overall tumor pain NRS≥1) and at least one post-baseline assessment, pain scores decreased by at least 2 points in 81.3% (13/16) pts, and pain scores reduced to 0 points (indicating no pain sensation) in 81.3% (13/16) pts, signifying clinically meaningful improvement. 43 pts (93.5%) experienced TRAEs with grade ≥3 TRAEs occurred in 8 pts (17.4%), including dermatitis acneiform (4.3%), folliculitis (4.3%), pneumonia (2.2%), upper respiratory tract infection (2.2%), ejection fraction decreased (2.2%), and blood creatine phosphokinase increased (2.2%). 2 pts (4.3%) reported treatment-related serious adverse events (one case of dermatitis acneiform and pneumonia each). No TRAEs resulting in dose reduction, discontinuation or death. Conclusions: FCN-159 demonstrated good tolerability and exhibited notable anti-tumor activity in pediatric pts with NF1-related PN. Clinical trial information: NCT04954001 . [Table: see text]

Background. Low-fluence Q-switched Nd: YAG laser (LF-QSNY) and picosecond 755 nm alexandrite laser (PSAL) have shown superiority in the treatment of nevus of Ota (NO). Objective. To compare the efficacy and safety of PSAL and LF-QSNY in the treatment of NO. Methods. 15 patients randomly underwent split-lesion treatment of the two lasers within three months. The visual analogue scale (VAS) was used to evaluate the efficacy outcomes. The patient's preferences, recurrence rate, and adverse events were also documented. Results. Fifteen patients with 34 lesions finished the trial. Lesions, operated with LF-QSNY and PSAL, reached VAS scores of 3.47 +/- 0.67 and 3.51 +/- 0.87, respectively ( P > 0.05 ). Most significant improvement in LF-QSNY was achieved after the first session (VAS = 1.84). One (6.67%) patient experienced a relapse on the PSAL side. Temporary hypopigmentation and hyperpigmentation mainly occurred on the PSAL side. Patients under five years demonstrated superior efficacy (3.81 +/- 0.47 vs 3.08 +/- 0.66, P = 0.046 ) than those over with the treatment of LF-QSNY. Limitations. Limited sample and lack of objective evaluation. Conclusion. The difference between the LF-QSNY and PSAL in the treatment of NO was statistically insignificant, while LF-QSNY may be a better choice for the treatment of early NO. This trial is registered with ChiCTR1900022690.

Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

10023 Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease characterized by multiple progressive tumor and non-tumor manifestations, with abnormal activating MAPK pathway. Plexiform neurofibromas (PN) presents in 20-50% of NF1 patients (pts) and may cause serious complications. Selumetinib was approved for pediatric pts with NF1-related PN in US and EU, but therapeutic options remain limited in China. FCN-159 is a highly potent selective anti-tumorigenic inhibitor of MEK1/2, potentially effective in NF1-related PN. Methods: This multi-center, open-label phase1/2 clinical trial is the first-in human study to assess safety and efficacy in pediatric pts with NF1-related PN. The primary objective was to determine the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D) in the dose escalation, followed by a dose expansion phase 2 to evaluate safety and efficacy. The starting dose in pediatric pts was determined according to the adults in the dose-escalation phase (previously published in ASCO 2022, abstract no. 3011). Here, we first present the safety and efficacy results in pediatric participants. Results: As of data cut-off (November 21, 2022), 65 pts were enrolled, 19 pts in phase 1 and 45 pts in phase 2. A dose of 4 mg/m 2 (10 pts) and 5 mg/m 2 (9 pts) were evaluated in phase 1 and no DLT was observed. Pediatric pts in the 5 mg/m 2 cohort achieved similar exposure to the 8 mg adult cohort. AUC simulation from population PK model at different BSA ranges were also similar to the adults of 8 mg. Therefore, the RP2D was determined to be 5 mg/m 2 .Treatment-emergent adverse events (TEAEs) were reported in 62 pts (95.4%). Common TEAEs (≥ 20%) were mouth ulcer (43.1%), sinus arrhythmia (36.9%), upper respiratory tract infection (35.4%), folliculitis (21.5%), paronychia (21.5%), and increased blood creatine phosphokinase (20%). 5 pts (7.7%) experienced grade ≥3 treatment-related AEs (TRAEs), including 2 pts (2/10, 10%) in the 4 mg/m 2 group and 3 pts (3/55, 5.5%) in the 5 mg/m 2 group. Grade 3 TRAEs were increased aspartate aminotransferase (1.5%), electrocardiogram QT prolongation (1.5%), folliculitis (3.1%), and dermatitis acneiform (1.5%). No grade ≥ 4 TRAEs were observed. 2 pts (3.1%) reported treatment-related serious adverse events (one case of rhabdomyolysis and dermatitis acneiform each). TEAEs led to dose interruption (26.2%), and discontinuation (1.5%). No reported TEAE led to dose reduction or death. Of the 19 pts with at least one tumor assessment data after baseline, 8 (42%) pts had partial response, 11 (57.8%) with stable disease and none with disease progression. The median DOR could not be evaluated. Conclusions: Overall, FCN-159 was well-tolerated and demonstrated promising anti-tumor activity in pediatric participants with NF1-related PN. Long-term efficacy and safety follow-up are ongoing. Clinical trial information: NCT04954001 .

3103 Background: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disease characterized by elevated RAS-mitogen activated protein kinase (MAPK) signaling that causes tumors to grow along the nerves. There is currently no medical cure for adult patients (pts). Plexiform neurofibromas (PN) is present in 20-50% of NF1 pts and may cause serious complications. FCN-159 is a highly potent anti-tumorigenic agent that functions via selective inhibition of MEK1/2. This study assessed the safety and efficacy of FCN-159 in adult NF1 pts with PN. Methods: This was a multi-center, open-label, single-arm phase 1 dose-escalation (data have been published in ASCO 2022, abstract no. 3011) and phase 2 dose-expansion study. Participants with NF1-related PN that was not completely resectable or not suitable for surgery were enrolled in the study to receive FCN-159 monotherapy continuously on a 28-day cycles. Herein, we report the safety and clinical efficacy of adult participants in both phase 1 and phase 2. Results: As of November 21, 2022, 82 pts were enrolled, including 19 pts in phase 1 and 63 pts in phase 2. The median follow-up was 10.2 months (range 9.4-11.0 months) at the data cut-off. All pts received more than one dose of FCN-159 and 78 had at least one tumor assessment based on REiNS critiera. A total of 26 (33%) pts had achieved partial response (PR) as best response, 51 (65%) pts had stable disease (SD), and only one pt was not evaluable for not meeting the minimum SD requirement of at least 16 weeks. The overall response rate (ORR) was 31.7% (95% CI: 21.9-42.9%). After 6-8 cycles of treatment, 68.2% (15/22) of pts with definite tumor pain (NRS-11 score≥2 points) at baseline had a decrease in pain intensity of at least 2 points at C7/C9 assessment. Pain scores decreased by an average of 2.7 points across all 22 pts. A total of 82 (100%) pts experienced treatment emergent adverse events (TEAEs). The most common TEAEs (≥ 20%) included folliculitis (69.5%), mouth ulcer (47.6%), diarrhea (41.5%), paronychia (41.5%), alopecia (32.9%), elevated lactate dehydrogenase (30.5%), elevated alkaline phosphatase (29.3%), tricuspid insufficiency (26.8%), and mitral insufficiency (26.8%). The most common grade ≥3 TEAEs were folliculitis (25.6%), paronychia (4.9%). There were no grade ≥ 4 treatment-related adverse events. One pt (1.2%) experienced a serious adverse event (duodenal ulcer) considered related to the study drug. 9.8% reported TEAEs leading to dose reductions, and 12.2% reported TEAEs leading to discontinuation. No death occurred during the study. Conclusions: Overall, FCN-159 has a manageable safety profile and demonstrated evidence of anti-tumor activity in the adult population with NF1-related PN. These promising findings warrant further investigation with long-time follow-up. Clinical trial information: NCT04954001 .

Background Currently, malignant peripheral nerve sheath tumors (MPNST) are the subject of intense research interest. However, bibliometric studies have not been conducted in this field. The purpose of the study was to identify historical trends and presents a bibliometric analysis of the MPNST literature from 2000 to 2022. Methods For the bibliometric analysis, publications were retrieved from the Web of Science database based on the following search terms: [TI = (MPNST) OR TI= (malignant peripheral nerve sheath tumors) AND PY = (2000–2022)]. The following information was collected for each document: the publication trends and geographical distribution, important authors and collaboration, keyword distribution and evaluation, most popular journals, and most influential articles. Results We included 1400 documents for bibliometric analysis, covering five categories: 824 articles, 17 proceedings papers, 68 letters, 402 meeting abstracts, and 89 reviews. Corrections, editorials, book chapters, data papers, publications with expressed concerns, and retractions were excluded from our research. Conclusion Since 2000, the number of publications on MPNST has continuously increased. Among all countries that contributed to the MPNST research, the USA, Japan, and China were the three most productive countries. The journal Modern Pathology has the most publications on MPNST, while those in the Cancer Research journal were the most frequently cited. The University of Texas MD Anderson Cancer Center may be a good partner to collaborate with. Recent research trends in MPNST have focused on tumorigenesis, clinical management, and predictive biomarkers.

Guo, Chengrui MD; Cen, Qingqing MD; Hu, Xiaojie MD; Lin, Xiaoxi PhD, MD Author Information

Neurofibroma is a benign tumor originating from Schwann cells. It is diagnosed as a symptom of neurofibromatosis type 1 (NF1) or solitary neurofibroma. Neurofibromatosis type 1 belongs to a class of hereditary diseases, whereas solitary neurofibroma is not. Presence of germline NF1 gene mutations can be used to distinguish the 2 conditions. However, due to false negative results in gene tests, NF1 may be misdiagnosed as solitary neurofibroma. This calls for development of more accurate diagnostic methods. The authors report 2 patients with neurofibroma who required surgery and fertility consulting. using primary cell culture and next-generation sequencing experiments, the authors found NF1 mutation in neurofibroma Schwann cells. But this mutation was not exit in peripheral blood, hence demonstrate this NF1 mutation was somatic rather than germline. These results confirmed the diagnosis of solitary neurofibroma rather than NF1. The presented method is, therefore, suitable for fertility consultation and diagnosis of solitary neurofibroma patient.

目的 探索和总结激光对神经纤维瘤瘤体表面色素增多的临床治疗效果.方法 回顾性分析自2017年11月至2022年7月,于上海交通大学医学院附属第九人民医院激光美容科接受激光治疗的10例神经纤维瘤瘤体表面色素增多患者,激光包括755 nm皮秒翠绿宝石激光,Q开关755 nm翠绿宝石激光,低能量Q开关1064 nm和/或长脉宽755 nm翠绿宝石激光.3名医师依据治疗前后的照片进行治疗改善视觉模拟(visual analogue scale,VAS)评分,同时记录患者病灶复发和不良反应发生情况.结果 10例患者病灶经2～10次激光照射治疗,改善评分为(2.93±1.13)分(1～4)分,平均清除率>50％.随访时间为(30.28±16.90)个月(9.21～56.95)个月,总体复发率为20％,无严重不良反应发生.结论 激光治疗神经纤维瘤瘤体表面色素增多是安全有效的,多次治疗可明显改善患者外观.此外,长脉宽755 nm翠绿宝石激光可用于改善病灶合并的异常毛发生长.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

3011 Background: Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease that increases susceptibility to malignant tumors. Up to 50% of patients with NF1 present with plexiform neurofibroma (PN). Surgery, a common treatment strategy for patients with PN, has limited efficacy. NF1 is caused by mutations in the gene that encodes neurofibromin; the NF1 mutation then leads to tumorigenesis via dysregulation of the Ras/Raf/MEK/ERK pathway. FCN-159 is anti-tumorigenic via highly potent, selective inhibition of MEK1/2. This study aims to assess the safety of FCN-159 in patients with NF1-related PN. Methods: This is a multicenter, open-label, single-arm, phase 1 dose-escalation and phase 2 dose-expansion study (NCT04954001). Patients with NF1-related PN that was not completely resectable or not suitable for surgery were enrolled in the study; they received FCN-159 monotherapy continuously in 28-day cycles. Here, we report safety and clinical efficacy data from adults enrolled in phase 1. Results: As of the data cutoff of December 1, 2021, 19 adults from 3 hospitals in China have been enrolled in the phase 1 dose-escalation study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. The most common neurofibroma-related complications were disfigurement and pain, occurring in 10 patients (52.6%) and 4 patients (21.1%) at baseline, respectively. Four patients experienced dose-limiting toxicity; G3 folliculitis was reported in 1 patient (16.7%) receiving the 8-mg dose and 3 (100%) patients receiving the 12-mg dose. The maximum tolerated dose was determined to be 8 mg. Study-drug-related treatment-emergent adverse events (TEAEs) were observed in all 19 patients (100%); the majority were grade 1 or 2 in severity. Nine (47.4%) patients reported grade 3 study drug-related TEAEs; 4 patients experienced paronychia and 5 experienced folliculitis, which were the most common causes of dose reduction (42.1%) and drug interruption (21.2%). One patient experienced a serious adverse event of rhegmatogenous retinal detachment, but this was considered unrelated to the study drug as it was preexisting at baseline. Of the 16 patients with at least 1 post-baseline tumor assessment, all (100%) had reduced tumor size and 6 (37.5%) had a reduction in tumor size of > 20%. Three out of 6 patients with a second tumor assessment result had further tumor shrinkage; tumor volumes in the remaining 3 patients were similar to those at first assessment. The largest reduction in tumor size was 84.2%. Conclusions: Overall, FCN-159 at 8 mg is well tolerated, with easy to manage adverse events, and showed promising anti-neurofibroma activity in phase 1; this warrants further investigation in a phase 2 study on efficacy and safety in this indication. Clinical trial information: NCT04954001.

Background Ethanol embolotherapy is considered an optimal choice for the treatment of arteriovenous malformations（AVMs）; however, there are some complications associated with this treatment. This study aimed to prospectively investigate systemic hemodynamic changes in high-flow AVMs using ethanol embolotherapy.Methods From September 2012 to September 2014, 34 male patients and 26 female patients with AVMs who underwent embolotherapy（100 sessions in total） with absolute ethanol were included in this study. Invasive systolic blood pressure（SBP） and heart rate（HR） were recorded before and after each injection and throughout the procedure. Differences between the initial and highest SBP（?maxSP） and HR values（?maxHR）, as well as the initial and final SBP（?SP） and HR（?HR） values, were analyzed. We aimed to explore the potential association between these values and the amount of ethanol that was used.Results The total ethanol used was variable（0.01–0.40 mL/kg; mean, 0.20 mL/kg）. SBP and HR increased after ethanol injection in most sessions（91 in 100 sessions）. SBP decreased in 9 sessions（9 in 100 sessions）, while HR, oxygen saturation, and end-tidal CO 2 decreased in one of the 9 sessions. ?maxSP and ?maxHR averaged 38.4 mmHg and 27.8 bpm, respectively（both P＜0.05）, while ?SP and ?HR averaged 3.4 mmHg and 4.0 bpm, respectively（both P＜0.05）. ?maxSP and ?maxHR were positively correlated with the total dose of ethanol injected.Conclusions Elevations in SBP and HR during ethanol embolotherapy are common, temporary, and most likely pain-mediated; these increases tend to be positively correlated with ethanol dose. Hypotension may be regarded as an acute complication of ethanol embolotherapy. Hypotension combined with bradycardia, oxygen desaturation, and decreased end-tidal CO 2 may be a potential predictor of cardiovascular collapse.

Background Impaired brow function in adult patients with arteriovenous malformation is a serious disability that can even influence the field of vision. Brow reanimation techniques are used to recover a more natural appearance and brow function. Many static procedures have been set to augment brow elevation, but only dynamic procedures can lead to better functional results. In this study, the experience of a single surgeon addressing the challenge of brow restoration with dynamic procedures is presented. Methods A retrospective review was performed using the records of 4 adult patients who underwent dynamic procedures using a soft tissue expander for brow restoration after arteriovenous malformation excision in the unilateral site of the forehead with the expander on the contralateral side. Movement and electrodiagnostic examinations were performed postoperatively at 2 months. Results The patients included 3 males and 1 female (mean age, 20.5 ± 4.04 years). Brow improvement was noted in all patients. The results of the electrodiagnostic examination showed synchronous and spontaneous motor unit potentials and compound muscle action potentials with the contralateral forehead. Conclusions Dynamic procedures using a soft tissue expander can provide both static and dynamic functional brow elevation of the contralateral frontalis and skin.

Objective:To screen regulatory genes of neurofibromatosis type 1 (NF1) involved in occurring and malignancy.Methods:The NF1-related gene expression data set (GSE14038) and methylation expression data set (E-GEOD21714) were obtained from the GEO public database. According to their sample sources, 10 cases were classified as normal samples and 48 cases were benign neurofibroma group and 19 cases of malignant peripheral nerve sheath tumor. The gene expression of different samples was analyzed to identify the differentially expressed genes, and the data were processed by applying gene annotation (GO), pathway enrichment analysis and protein interaction analysis (PPI) tools.Results:After comparing difference of gene expression and methylation. in the database, compared with normal group, there were 14 genes in the benign neurofibroma group that might be related to the occurrence of neurofibroma, and 105 genes in the malignant peripheral nerve sheath tumor group that might be related to malignant transformation. The main functions of the differential gene in the benign neurofibromatosis group are positive regulation of DNA dependent/directed transcription, transcription factor binding and mainly located in the spindle microtubules. The main function of the differential gene in the malignant neurofibroma group is regulation of cell proliferation, sequence-specific DNA binding and mainly located in the cell body of neuron. According to pathway enrichment analysis, the differential genes in the benign neurofibroma group were mainly enriched in sphingolipid metabolism, and the differential genes in the malignant neurofibroma group were mainly enriched in axonal guidance. Protein-protein interaction analysis of differential genes showed that the encoded proteins are mainly located in stem cell development, of which PAX3, PTGS2, SNAI2, MBP and NOG are the top 5 related expressed hub genes. Conclusions:PAX3 may be related to the occurrence of neurofibromatosis, while PTGS2, SNAI2, MBP and NOG may be related to the malignant transformation of MPNST.

Background: Orbit deformities are usually found in neurofibromatosis type 1 patients, especially those with orbital-periorbital plexiform neurofibroma (OPPN). Unfortunately, current morphometry is complicated and, in some cases, cannot be performed on the deformed orbit due to the destruction of landmarks. Herein, we present a novel 3-dimensional (3D) morphometry for these orbital measurements. Methods: We retrospectively reviewed 29 patients with OPPN, and another 29 disseminated cutaneous neurofibroma patients served as controls. All patients had undergone craniofacial computed tomography and 3D reconstruction. New morphometry was used to measure the area of the orbital rim (OR) and superior orbital fissure (SOF). Results: For the 29 patients with OPPN, the area of the OR at the affected side was 14.18 +/- 3.50 cm(2), while the OR at the nonaffected side was 12.32 +/- 1.38 cm(2). In addition, the area of the SOF at the affected side was 5.37 +/- 5.75 cm(2), while that at the nonaffected side was 1.27 +/- 1.03 cm(2). The OR and SOF at the affected side are more likely to become enlarged compared with those at the nonaffected side. Among the 29 patients with OPPN, the novel morphometry could be performed in 19 cases (65.5%) that cannot be measured by previous morphometry. Conclusion: The novel morphometry is convenient and reproducible, which optimizes its application in pathologic cases, especially those involving deformed orbits.

Fluorosis and bone pathologies can be caused by chronic and/or excessive fluoride intake. Despite this, few studies have been conducted on the cellular mechanisms underlying osteoblast toxicity in the presence of NaF. Here, we investigated the effects of fluoride on MC3T3-E1 cells. We showed that the proliferation of MC3T3-E1 cells was inhibited by exposure to NaF. In addition, apoptosis was induced by NaF, as caspase-associated proteins showed a higher level of expression and apoptotic bodies were formed. Furthermore, endoplasmic reticulum (ER) stress induced by NaF activated the unfolded protein response (UPR) and upregulated the expression of the glucose-regulated proteins 94 (GRP94) and 78 (BiP). Therefore, ER stress plays a vital role in NaF-induced autophagy and apoptosis. Furthermore, apoptosis is promoted following the inhibition of NaF-induced autophagy. In conclusion, under NaF treatment, the ER stress-signaling pathway is activated, leading to apoptosis and autophagy and affecting the proliferation and survival of MC3T3-E1 cells.

Background: Neurofibromatosis (NF) is an autosomal dominant genetic disorder, and NF type 1 (NF1) is one of the most common forms. Plexiform neurofibroma (PNF) is one of the characteristic expressions of NF1. The proper treatment for patients with craniofacial PNF is surgery. The evaluation methods for the surgical outcome of these patients are still controversial. As a consequence, a one-stage surgical technique and an appropriate evaluation method for patients with craniofacial PNF were discussed in this article. Methods: This research is a retrospective study. Nine patients with craniofacial PNF were included in this study. They had undergone a one-stage surgical technique of tumor debulking and nasolabial fold reconstruction. Three methods had been applied to evaluate the surgical outcome. Results: Significant improvement was observed in 8 patients. Eight patients were assessed by the relatively objective evaluation method. Obvious symmetry improvement was calculated using Mimics software in 7 patients. Conclusion: The surgical technique could achieve good surgical outcomes in both functional and cosmetic terms. Additionally, the relatively objective evaluation technique based on Mimics software could be a more convincing method for evaluating the surgical outcomes of craniofacial patients with PNF.