BackgroundIgG4-related disease (Immunoglobulin G4-related disease) is an immune-mediated condition characterized by elevated serum IgG4 levels, clinically presenting as multi-organ enlargement. However, only case reports exist of IgG4-related disease presenting initially with peripheral neuropathy. This study aims to elucidate the clinical features of IgG4-related disease with prominent peripheral neuropathy manifestations.MethodsWe reviewed 16 cases of IgG4-related disease with peripheral neuropathy as the initial presentation, including 15 cases from the literature and one case from our institution. Patient data were extracted and analyzed, encompassing clinical characteristics, pathological features, electrophysiological findings, and treatment information.ResultsThe median age of onset was 64.5 years, with 3 female and 13 male patients. Initially, 15 patients presented with limb numbness and weakness, while 1 exhibited hoarseness. All 16 patients demonstrated organ enlargement in addition to peripheral nerve damage. Peripheral nerve electrophysiology revealed demyelination and/or axonal lesions. All cases received oral corticosteroids, with immunosuppressants added in 3 cases. All patients responded well to corticosteroid therapy.ConclusionPeripheral neuropathy may present as the initial manifestation of IgG4-related disease. Such neuropathy demonstrates favorable response to corticosteroid therapy, and the indication for adding immunosuppressive agents should be evaluated based on individual circumstances.

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that mostly presents as sporadic cases. Currently, no mitochondrial-related gene mutations have been identified as the cause of ALS. Mitochondrial gene mutations cause rare hereditary diseases, and the symptoms of pure muscle weakness and muscle atrophy are rarely observed. CASE REPORT:We report the case of a young patient clinically diagnosed with ALS concurrently associated with a pathogenic mutation in the mitochondrially encoded nicotinamide adenine dinucleotide: ubiquinone oxidoreductase core subunit 6 (MT-ND6) gene. However, the pathogenic relationship between the MT-ND6 gene and ALS has not been confirmed. CONCLUSION:We provide a case report and a literature review aimed at increasing the understanding of the connection between the two. It is essential to consider the potential modifying role of mitochondrial pathogenic genes in ALS.

BACKGROUND AND PURPOSE:Antibiotics and ibuprofen combinations cause mitochondrial toxicity and hepatotoxicity. This study investigated whether dietary antioxidants could protect against this damage via protein kinase AMP-activated alpha (AMPKα)/nuclear factor erythroid 2-related factor 2 (NRF2) pathways. EXPERIMENTAL APPROACH:Human umbilical vein endothelial cells (HUVECs) were treated with antibiotics (kanamycin, azithromycin, ampicillin or ciprofloxacin) plus ibuprofen with or without antioxidants. Azithromycin/ibuprofen induced hepatotoxicity was evaluated in C57BL/6J mice. Mitochondrial parameters including morphology, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm) and key proteins (mitofusin 2, AMPKα, glycogen synthase kinase 3 beta [GSK3B], NRF2 and haem oxygenase 1 [HO1]) were analysed. KEY RESULTS:Antibiotics/ibuprofen combinations triggered mitochondrial fission, ROS overproduction and mitofusin 2 down-regulation. Four antioxidants, that is, coniferaldehyde, raspberry ketone, gastrodin and eugenol, restored mitochondrial function and morphology. Coniferaldehyde and raspberry ketone effectively prevented in vivo hepatotoxicity and inflammation. Moreover, coniferaldehyde/raspberry ketone activated NRF2/HO1 while restoring AMPKα/GSK3B signalling. CONCLUSIONS AND IMPLICATIONS:Coniferaldehyde and raspberry ketone showed potent rescue effects in vitro against all antibiotic models and in vivo against azithromycin/ibuprofen-induced hepatotoxicity through AMPKα-GSK3B/NRF2-HO1 modulation, with favourable safety profiles.

Background and ImportanceAnkylosing spondylitis (AS) is a systemic chronic inflammatory disease. Andersson lesion (AL) is a late complication of advanced AS. Idiopathic spinal cord hernia (ISCH) is a rare disorder of the spinal cord. However, according to our literature review, the simultaneous occurrence of AL together with ISCH in a single AS patient had never been reported.Clinical PresentationA 49-year-old male reported a 30-year history of thoracolumbar pain and limited mobility and was diagnosed with AS with dual complications of AL and ICSH. Before correction surgery, physical examination, x-ray, CT,MRI and Blood HLA-B27 examination were performed and a series of radiological parameters, including the degree of kyphosis and the T1-pelvic angle (TPA), were measured. Several days after surgery (Distal PSO was used), we performed examinations to check the patient's physical condition which showed the patient recovered remarkably. CTA was done, indicating that the patient's aorta moved anteriorly with the osteotomy side undamaged. A series of morphological parameters were measured again, including TPA, LL, and TK. CT and MRI were performed again, reflecting significant bone-to-bone fusion and successful recovery. The patient relieved the symptoms and regained his daily activities.ConclusionsWe deepen the understanding of the diagnosis and treatment of AS with rare complications of AL and ISCH. Distal PSO could be an effective option for severe AS patient.

Medulloblastoma (MB) is the most common malignant brain tumors in children. Sonic Hedgehog (SHH) subgroup of MB accounts for about 25% of all MBs. SMO inhibitors are used for target therapy. However, drug resistance and toxicity occurred. New therapeutic targets are urgently needed to be developed. Here, through RNA-sequencing and Nanostring Assay analysis of primary MBs, we screened out prolactin receptor (PRLR) as a gene with higher expression level in SHH-MB compared with other subgroups of the tumor. Long isoform of PRLR (PRLR-LF) played a pivotal role in promoting SHH-MB tumor invasion, enhancing the proliferation and colony formation ability. KEGG analysis showed that PRLR-LF expression has close relationship with p53 signal pathway in SHH-MB cells. High expression of CDK6 downstream of the p53 pathway was observed to have a high correlation with PRLR expression, indicating a poor prognosis of the tumor. In addition, PRLR was demonstrated to promote cell proliferation by regulating CDK6 through Ras-MAPK signal pathway in vitro. Synthesized recombinant Δ1-11-G129R-PRL, a competitive inhibitor of PRLR, interfered PRL-PRLR binding, could inhibit the regulation to CDK6, and could and inhibit the proliferative ability of SHH-MB tumor cells. In conclusion, we unveiled PRLR promoted SHH-MB tumor progression through signaling pathway besides the canonical SHH pathway. PRLR inhibitor shed light on a potential therapeutic value for SHH-MB patients.

STUDY DESIGN:A prospective case-control study. PURPOSE:This prospective case-control study aimed to analyze the paravertebral muscle changes in patients with adolescent idiopathic scoliosis (AIS) and determine paravertebral myopathological changes associated with the clinical progression of AIS. OVERVIEW OF LITERATURE:The incidence of AIS is significant globally and worsens before bone maturation, causing a serious effect. Many studies have investigated its causes-such as genetic, epigenetic, and hormonal factors-but more research remains warranted. METHODS:This study enrolled 40 patients with AIS, 20 patients with congenital scoliosis (CS), and 20 patients with spinal degenerative disease (SDD). All patients underwent open posterior surgery in our hospital, and a paravertebral muscle (multifidus muscle) biopsy was performed intraoperatively. This study included many indexes that describe muscle, especially dystrophin staining. The above pathological results were compared among the AIS, CS, and SDD groups. The correlation between the Cobb angle and Nash-Moe classification and the above pathological results was analyzed in patients with AIS. RESULTS:Significant reductions in the dystrophin staining of dystrophin-1 (p<0.001), dystrophin-2 (p<0.001), and dystrophin-3 (p<0.001) were observed in the AIS group than in the CS and SDD groups. The higher the Nash-Moe classification in the AIS group, the more significant the loss of dystrophin-2 (p=0.042) in the convex paraspinal muscles. Additionally, a significantly positive correlation was observed between the reductions of dystrophin-2 on the concave side of the AIS group and Cobb angle (p=0.011). CONCLUSIONS:Dystrophin protein deficiency in the paraspinal muscles plays a crucial role in AIS formation and progression. The severity of scoliosis in patients with AIS is correlated with the extent of dystrophin loss in the paravertebral muscles. Therefore, dystrophin dysfunction may be relevant to AIS occurrence and development.

Objective Summarize the pathological and clinical characteristics of muscle disorder cases with nemaline-shaped structure,to improve the diagnosis and differential diagnosis of the disease.Methods and Results A total of 22 cases with nemaline-shaped structure underwent muscle biopsy were selected from May 2021 to May 2024.As to final diagnosis,there were 3 cases(13.64%)of congenital nemaline myopathy,12 cases(54.54%)of amyotrophic lateral sclerosis(ALS),2 cases(9.09%)of limb-girdle muscular dystrophy(LGMD),one case(1.45%)of desminopathy,one case(1.45%)of charcot-marie-tooth disease(CMT),one case(1.45%)of non-specific myositis,one case(1.45%)of frontotemporal dementia(FTO)caused by GRN,and one case(1.45%)of hypothyroid myopathy.The muscle biopsy of all 22 cases revealed various granular,rod-shape or flaky purplish-red depositions in the sarcoplasm as nemaline-shaped structure in modified Gomori trichrome(MGT)staining and positive immunohistochemistry staining of myotilin and/or α-actin.Under electron microscopy,some cases had the ultrastructural characteristics of nemaline body or nemaline-shaped structure.Muscle biopsy that confirmed congenital nemaline myopathy had more typical nemaline,besides myotilin and α-actin were both immunopositively.Besides nemaline myopathy,the pathological changes of other muscle diseases also had specific characteristics,such as neurogenic atrophy was often present in ALS;abnormal aggregation of desmin protein was often present in desminopathy;circular atrophy,large amount internalized nuclei and interstitial fibrosis were often present in LGMD;in addition,obvious inflammatory cell infiltration was common in non-specific myositis.Therefore,the diagnosis of nemaline myopathy could not be relied on HE staining and electron microscopy alone.Apart from 14 patients that diagnosed with ALS,non-specific myositis and hypothyroid myopathy,NEB gene mutation(3 cases),CAPN3 gene mutation(one case),DYSF gene mutation(one case),SH3TC2 gene mutation(one case),GRN gene mutation(one case),and DES gene heterozygous mutation(one case)were detected by whole exome sequencing(WES)in the remaining 8 cases.Conclusions Nemaline-shaped structure can appear in a variety of muscular disorder and neurodegenerative diseases.Combined with clinicopathological characteristics are contribute to recognize nemaline myopathy,and the genetic test by WES is strong evidence for nemaline myopathy.

In pneumonia, the deficient or delayed pathogen clearance can lead to pathogen proliferation and subsequent overactive immune responses, inducing acute lung injury (ALI). While screening human genome coding genes using our peripheral blood cell chemotactic platform, we unexpectedly find SLP adaptor and CSK interacting membrane protein (SCIMP), a protein with neutrophil chemotactic activity secreted during ALI. However, the specific role of SCIMP in ALI remains unclear. In this study, we investigate the secretion of SCIMP in exosomes (SCIMP exo ) by macrophages after bacterial stimulation, both in vitro and in vivo. We observe a significant increase in the levels of SCIMP exo in bronchoalveolar lavage fluid and serum of pneumonia patients. We also find that bronchial perfusion with SCIMP exo or SCIMP N-terminal peptides increases the survival rate of the ALI model. This occurs due to the chemoattraction and activation of peripheral neutrophils dependent on formyl peptide receptor 1/2 (FPR1/2). Conversely, exosome suppressors and FPR1/2 antagonists decrease the survival rate in the lethal ALI model. Scimp -deficient and Fpr1/2 -deficient mice also have lower survival rates and shorter survival times than wild-type mice. However, bronchial perfusion of SCIMP rescues Scimp -deficient mice but not Fpr1/2 -deficient mice. Collectively, our findings suggest that the macrophage-SCIMP-FPRs-neutrophil axis plays a vital role in the innate immune process underlying ALI.

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by xanthomatous infiltration of affected organs. We present a case of a 62-year-old man with ECD initially presenting with constrictive pericarditis. Comprehensive imaging revealed systemic involvement, including the skeleton, orbit, pituitary, lung, kidney, and retroperitoneum, despite the absence of related symptoms. The diagnosis of ECD was eventually confirmed through histopathological evidence from a CT-guided biopsy. The patient responded well to interferon-α2b treatment, with gradual symptom amelioration and improvement in imaging and laboratory findings over a 5-month follow-up period. This case highlights the importance of considering ECD in the differential diagnosis of constrictive pericarditis and the utility of multimodal imaging for accurate diagnosis and management of this rare disease. The patient's positive response to treatment also highlights the potential for effective management of ECD, particularly with early diagnosis and intervention.

BackgroundNeuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date.Case presentationWe present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of NOTCH2NLC.ConclusionThis case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy.

Granulomatous myopathy (GM) is a rare disease characterized by non-caseating inflammation of the skeletal muscle, with sarcoidosis as a common cause. Here, we report a case of GM co-existent immune-mediated necrotizing myopathy (IMNM) in which an anti-signal recognition particle (SRP) antibody was positive and a muscle biopsy showed a non-caseating granulomatous structure, along with myofiber necrosis and inflammatory cell infiltration.

目的 探讨神经内神经束膜瘤(intraneural perineurioma,InP)的临床病理学特征.方法 回顾性分析16例InP的临床病理学及免疫表型特征,并复习相关文献.结果 16例InP患者中男性5例,女性11例,年龄5～56岁,平均年龄27.4岁,14例为单发病变(分别位于尺神经、正中神经、桡神经、腓总神经),2例为多发病变(分别位于双侧臂丛神经及C1-3神经根).患者术前病程2～360个月,常表现为病变神经对应区域缓慢进展的运动功能障碍,部分有感觉功能异常;影像学提示局部神经增粗呈纺锤形或长梭形,边界尚清,肌电图提示周围神经损伤;光镜下见梭形的神经束膜细胞以轴突-施万细胞复合体为中心形成假洋葱球样结构.电镜下见长而细的神经束膜细胞胞质内富含吞噬囊泡,与其伴随的施万细胞一起围绕轴突呈同心圆状排列.免疫表型:神经束膜细胞EMA、Glut-1、Claudin-1阳性,中心的轴突-施万细胞复合体NF、S-100及SOX10阳性.Ki-67增殖指数＜5％.结论 InP是一种罕见的起源于神经束膜的良性肿瘤,易与肥大性周围神经病、腓骨肌萎缩症、混杂性神经鞘膜肿瘤、神经鞘瘤、神经纤维瘤等混淆,熟练掌握其特征性的组织学表现及免疫表型是诊断关键.

目的 探讨伴IDH1 R82K突变的复发性胶质瘤的分子特征及鉴别诊断.方法 回顾性分析 1 例伴IDH1 R82K突变的复发性胶质瘤的临床病理资料,采用免疫组化EnVi-sion及分子检测,并复习相关文献.结果 患者女性,33 岁,左侧额叶切除术后3 年,复发2 次,手术2 次,第1 次手术标本可见肿瘤细胞丰富,细胞密度高,细胞大小一致,核圆形居中,核周有空晕,核分裂象易见,一代测序检测出 IDH1 R132H和R82K 突变、TERT 启动子突变,FISH 检测出 1p/19q共缺失;第2 次手术标本可见部分区域细胞密度较高,与星形胶质细胞形态类似,细胞核圆形或椭圆形,异型性较小,核分裂象罕见,局灶可见点灶状坏死及点灶状出血,一代测序仅检测出 IDH1 R82K 突变,二代测序检测出 CIC 及MYCN基因突变,FISH未检测出 1p/19q共缺失.结论 胶质瘤复发可发生类型和分子特征的改变,且复发胶质瘤需与治疗后的改变进行鉴别.

Background GNE myopathy is a rare distal myopathy caused by mutations of the GNE gene. A few cases of GNE myopathy accompanied by neurogenic features of electrophysiology mimicking hereditary motor neuropathy were reported recently. We confirmed this feature and described the clinical phenotype and mutations of GNE myopathy in these rare cases. Results The absence of lower limb tendon reflexes, decreased compound muscle action potentials in lower leg motor nerves, and neurogenic pattern of electromyography suggested neuropathy in four patients. However, muscle pathology revealed a predominantly myogenic pattern. The follow-up electroneurography results implied that the compound motor action potential amplitudes deteriorated over time. Next-generation sequencing identified three novel variants of the GNE gene, c.2054T > C (p.Val685Ala), c.424G > A (p.Gly142Arg) and c.944T > C (p.Phe315Ser), as well as two hotspot mutations, c.115C > T(p.Arg39*) and c.620A > T(p.Asp207Val), in these patients. These novel mutations cosegregated with disease in the family. Conclusions These rare cases supported the existence of neurogenic features of electrophysiology different from the typical myopathic pattern of GNE myopathy.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is composed of at least four molecular subgroups with distinct clinical characteristics. The sonic hedgehog (SHH) subgroup exhibits the most abundant tumor-associated microglia/macrophages (TAMs) infiltration. SHH-MB patients treated by anti-SHH drugs showed high drug resistance. However, the comprehensive role of TAMs in SHH-MB remains enigma. The aim of this study is to explore the mechanism of TAM activation/polarization in SHH-MB and discover a potential immunotherapeutic target to reduce drug resistance. We first analyzed expression profiles of immuno-microenvironment (IME) in four subgroups of 48 MB tumors using NanoString PanCancer IO360 panel and found TAMs were the major component of IME in SHH-MBs. We further distinguished M1/M2-like TAMs in tumors and found M2-like macrophages, rather than microglia, were enriched in SHH-MBs. In transgenic SHH-MB mice, these TAMs had close relationship with tumor progression. Polarization of the TAMs could be induced by MB-derived exosomes in vitro. We then screened SHH MB-derived exosomal miRNAs and their target genes using RNA sequencing and luciferase assay to clarify their roles in regulating TAM polarization. We found down-regulated let-7i-5p and miR-221-3p can induce M2-like polarization of TAMs via upregulating peroxisome proliferator activated receptor gamma (PPARγ). Finally, we demonstrated the PPARγ antagonist efficiently improved the antitumor activity of SMO inhibitor in vivo, which may be related to inhibition of M2-like TAMs. Our findings suggest a potential therapeutic strategy for SHH-MB by targeting tumor-supportive M2-like TAMs to enhance the therapeutic effect of SMO inhibitors.

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of non-neoplastic histiocytes that contain intracytoplasmic crystallized immunoglobulins. Although CSH can occur in various organs, gastric CSH is very rare. Therefore, diagnosing gastric CSH remains a challenge. Here, we present the case of a 69-year-old man with localized gastric CSH who presented with positive fecal occult blood for 2 days. Gastroscopy showed that there was a piece of irregular whitish focus in the big bend of the gastric antrum, which was soft and elastic. Histologically, the biopsied gastric mucosa showed chronic inflammation, mild activity with erosion, and numerous eosinophilic mononuclear cells containing fibrillary crystalloid inclusions in the lamina propria. Immunohistochemically, these crystal-containing cells were positive for CD68/PGM1 and Igk, which revealed that the cells were histiocytes harboring kappa light chain-restricted immunoglobulin crystals. Electron microscopic examination showed numerous high-electron-density particles in the cytoplasm of cells, with crystal structures of different sizes and shapes. This case highlights how immunohistochemistry can help with differential diagnosis and classification.

BACKGROUND:Scoliosis is a complex three-dimensional deformity of spine and one of the common complications of collagen VI-related myopathy, caused by mutations in collagen type VI alpha 1 chain (COL6A1), COL6A2, and COL6A3 genes. The typical clinical presentations of collagen VI-related myopathy include weakness, hypotonia, laxity of distal joints, contractures of proximal joints, and skeletal deformities.CASE SUMMARY:A 28-year-old female presented with scoliosis for 28 years without weakness, hypotonia, laxity of distal joints, and contracture of proximal joints. Computed tomography and magnetic resonance imaging revealed hemivertebra, butterfly vertebra, and the missing vertebral space. Patients underwent orthopedic surgery and paravertebral muscle biopsy. The Cobb angle dropped from 103.4° to 52.9°. However, the muscle biopsy showed neurogenic muscular atrophy with myogenic lesions, suggesting congenital muscular dystrophy. Gene analysis indicated that mutations in COL6A1 (c.1612-10G>A) and COL6A2 (c.115+10G>T, c.2749G>A). Immunohistochemistry staining for collagen VI displayed shallow and discontinuous. Eventually, the patient was diagnosed as collagen VI-related myopathy.CONCLUSION:This newly found subtype of collagen VI-related myopathy has no typical manifestations; however, it is characterized by severe scoliosis and congenital vertebral deformity.

目的 探讨散发性Creutzfeldt-Jakob病(克雅病,sCJD)的临床表现和影像学特点,随访生存期,以期更好地指导临床诊断.方法 对北京大学第三医院神经内科2002年1月至2020年12月收治的9例sCJD患者进行回顾性分析.结果 患者发病年龄为(62±10)岁;最常见的症状包括无动性缄默7例(7/9),肌阵挛发作6例(6/9),反应迟钝5例(5/9),共济失调4例(4/9),精神行为异常、言语混乱3例(3/9),行走不稳3例(3/9).首发症状以反应迟钝,精神行为异常为主.磁共振弥散加权成像皮层高信号6例(6/9),脑脊液14-3-3蛋白4例(4/9),基底节异常高信号3例(3/9),脑电图三相波1例(1/9).中位生存期4个月,24个月随访生存2例(2/9).结论 本研究中,sCJD中老年发病,首发症状无特异性,弥散加权成像皮层、基底节高信号检出率高,中位生存期较短.

Background : Adolescent idiopathic scoliosis (AIS) is characterized by vertebral rotation and lateral curvature of the spine and affects 2-4% of the population throughout the world and the cause of the disease is still controversial. Recent researches suggest that there is an internal correlation between certain neuromuscular diseases and AIS. This study aims to characterize the paraspinal muscles of AIS patients, and to further explore the its etiology. Methods: Eighteen AIS patients treated with posterior scoliosis correction surgery were included and had biopsies taken from the paraspinal muscle at the apex vertebra region. Serial sections with conventional H&E staining and histochemical staining were obtained, and immunohistochemical examinations were employed to detect Dystrophin-1, -2, -3, Myosin, MHC-1, CD4, CD8, CD20, and CD68 or CD163 antibodies. Biopsy samples were grouped according to the subjects’ Cobb angle and Nash-Moe’s classification respectively, and the corresponding pathological changes were compared between groups. Results: The immunohistochemical staining results showed significant differences in the expression pattern of Dystrophin-2 (P=0.023) and Dystrophin-total (P=0.018) between the mild and severe scoliosis groups, with the expression of Dystrophin more abnormal or absent in the severe scoliosis group. There were also significant differences in the expression pattern of Dystrophin-2 (P=0.035) between the Nash-Moe classification subgroups. The expression of Dystrophin-3 was absent to various extent in all patients. Besides, we observed an infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons. In all patients, the expression of MHC-1 on myolemma was present in some muscle fibers. Conclusions : The expression of dystrophin protein was significantly reduced and was correlated with the severity of scoliosis, suggesting that dystrophin protein dysfunctions contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS mainly manifested in T cell activation and infiltration, and there seemed to be certain correlations between the expression of MHC-1 and the abnormal expression of dystrophin protein. Further studies along these results may open up new ideas for the diagnosis of scoliosis and the treatment for paraspinal myopathy.

Medulloblastomas (MBs) are currently divided into 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Among them, Group 3 MB has the worst prognosis, and 40%-50% of Group 3 cases are already metastatic at the time of diagnosis. Emerging evidence indicates that exosomes drive tumor invasion, but very little is known about exosomes in MBs. In this study, we initially discovered that exosomes isolated from Group 3 MB cell lines altered in vitro behaviors of a less invasive SHH MB cell line and yielded a much more aggressive phenotype. RNA-sequencing analysis revealed 7 exosomal miRNAs with markedly different expression levels between the SHH and Group 3 MB cell lines. They were all predicted to be related to the Ras/MAPK pathway according to the Kyoto Encyclopedia of Genes and Genomes data analysis. Increased expression of miR-181a-5p, miR-125b-5p, and let-7b-5p was further confirmed in Group 3 MB cells with real-time PCR and was shown to increase in vitro invasion and migratory abilities of tumor cells through the activation of ERK in Ras/MAPK pathway. Collectively, our findings suggest that exosomal miRNAs have a critical role in MB progression in vitro and might serve as diagnostic biomarkers and therapeutic targets.