Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment

Objective:To analyze the clinical phenotype and genotype characteristics of infantile spasm (IS) associated with UBA5 gene mutation. Methods:Four cases of IS caused by UBA5 gene variation diagnosed at the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were retrospectively analyzed.The clinical manifestations, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), treatment, and follow-up results were summarized. Results:In this study, 4 cases (3 males and 1 female) were clinically diagnosed with IS and carried complex heterozygous variation of UBA5 gene.Genetic analysis confirmed that a total of 6 different mutation sites were found, five of which were unreported.All the 4 cases presented with epileptic spasms at the age of 1 d to 8 months after birth, and 2 cases had focal seizures during the course of disease.The EEG of 4 cases showed hypsarrhythmia and cluster or isolated epileptic spasms were detected.Of the 3 patients who had brain MRI results, 2 cases showed nonspecific abnormalities and 1 case was normal.All the 4 patients had developmental delayed before seizure onset, and regressed to varying degrees and made slow progress after onset.One case had microcephaly, and 3 cases had hypertonia.At the last follow-up, the age of the 4 patients ranged from 7 months to 6 years and 4 months.All 4 patients were treated with multiple antiepileptic drugs, but none of them were under control. Conclusions:Children with IS associated with UBA5 gene variation have an early onset age, often accompanied by developmental delayed, microcephaly, dystonia, and refractory seizures.

Objective:To analyze the clinical phenotype and genetic characteristics of children with germline PIGA gene mutations. Methods:The clinical presentations, blood biochemistry, electroencephalogram (EEG), brain magnetic resonance imaging (MRI) and genetic test results of 10 children diagnosed at the Department of Pediatrics of Peking University First Hospital between January 2014 and June 2020 were analyzed.Results:All these 10 children were male, with seizures and severe developmental delay.Five out of eight cases showed hypotonia.Four out of nine cases had facial deformity or multiple organ abnormalities.The onset age of seizures ranged from one month and 28 days to 10 months, with an average age of 4.8 months.There were various types of seizures, and all patients showed focal seizures.The seizures of 6 patients in these 10 cases could be induced by fever disease.Diffuse slow waves mixed focal or multifocal discharges of interictal EEG in 9 cases with PIGA-deficient.Brain MRI showed enlarged subarachnoid space in 44.4% (4/9 cases) of patients.Slight elevated serum alkaline phosphatase could be seen in 2 cases.Genetic analysis confirmed that a total of 8 different mutation sites were found, 7 of which were unreported.In this group, 4 cases were diagnosed with multiple congenital anomalies -hypotonia -seizures syndrome 2 (MCAHS2), 5 cases were diagnosed with developmental delay and epilepsy without deformity, and one case was not classified, respectively. Conclusions:Focal seizure was common in these patients with PIGA mutations, and often induced by fever disease.Interictal EEG was characterized by diffuse slow waves mixed focal or multifocal discharges.Enlarged subarachnoid space was the most common brain MRI abnormality in these patients.The phenotype of patients only partially conformed to typical MCAHS2 manifestations, and most of them had no deformity.

Objective: To investigate the genotype and phenotype of children with KCNA2 gene related developmental and epileptic encephalopathy (DEE). Methods: Clinical data including the manifestations and electroencephalogram of 8 children with KCNA2 variants treated in the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were collected and analyzed retrospectively. Results: Among the 8 epileptic patients with KCNA2 variants, 5 were males and 3 were females. The age of onset was from 1 day to 11 months. The age at last follow-up ranged from 4 months to 86 months. Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified. The variant of c.1214C>T was found in six patients (case 1-6). For these patients, the age of onset was from 5 to 11 months and they were characterized by multiple seizure types. All had focal seizures and had normal development before seizure onset with developmental regression after seizure onset. The first electroencephalogram showed epileptic discharges in Rolandic region in two, epileptic discharges in Rolandic region combined with generalized discharge in one, generalized discharge with posterior predominance in two (combined with or transferred to Rolandic region during the course) and epileptic discharges in posterior region combined with generalized discharge in one. And in 5 of them the Rolandic discharges developed into epileptic electrical status (ESES) during sleep. All the six patients were still treated with a combination of multiple antiepileptic drugs. Two of them had seizure controlled at 80 months and 68 months, respectively. The variant of c.1120A>G were identified in two of eight patients (case 7 and 8) and they had seizure onset on the 1st day after birth. Their epileptic seizures were frequent and difficult to control. They had remarkably developmental delay and microcephaly since birth. One case (case 8) had a wide forehead. They had frequent seizures up to the last follow-up. In case 7, the early electroencephalogram showed epileptic discharges in temporal region, and interictal electroencephalogram at 3 months of age showed multifocal discharge with posterior and temporal region predominance. In case 8, the early electroencephalogram was normal and electroencephalogram showed burst suppression at 2 months of age, and it developed epileptiform discharge in posterior region at 1 year of age. Conclusions KCNA2 gene variants can lead to DEE with multiple seizures types. Among them, loss-of-function c.1214C>T is the most common, and these patients have seizure onset at infancy with Rolandic discharges tended to develop into to ESES pattern. The variant of c.1120A>G is a gain-of- and loss-of-function variant, patients with c.1120A>G have seizure onset in neonatal period, the phenotype overlaps with the former but is more severe.

Objective: To investigate the electroclinical findings in epilepsy children with epileptic negative myoclonus (ENM) restricted to the lower limb as the first seizure type. Methods: Each retrieved electroencephalogram record performed between March 2011 and March 2018 at the Department of Pediatrics of Peking University First Hospital was searched with "midline" . There were 302 records of 175 patients with "benign" or "functional" midline spikes. A retrospective review of each patient′s hospital record was performed. Thirteen patients had ENM restricted to the lower limb as the first seizure type. The clinical and electroencephalogram characteristics of them were analyzed. Results: Thirteen patients manifested ENM restricted to the lower limb as the first seizure type, diagnosed as benign childhood focal epilepsy with vertex spikes (BEVS). Six patients had ENM as the first and only seizure type during the short-time follow-up. Among them, there were 1 male and 5 females. The age at seizure onset was (2.5±0.7) years. One of them had electrical status epilepticus during sleep (ESES) identified on electroencephalogram at theage of 4 years and 8 months. The last follow-up age was (3.8±1.5) years. The remaining 7 patients developed nocturnal focal motor seizures. Among them, there were 4 males and 3 females. The age at seizure onset was (3.5±0.7) years. Two of them were diagnosed as BEVS evolving into benign childhood epilepsy with centrotemporal spikes (BECTS) and 5 were diagnosed as BEVS concurring with BECTS. The age at focal seizures was (4.1±0.6) years. The interval ranged from 1 month to 1 years. Six of 7 patients had electrical ESES with the age of (5.2±1.0) years. All had developmental regression, further diagnosed as atypical benign partial epilepsy (ABPE). The median age at last follow-up was 5.9 years. Five of 13 patients had repeated electroencephalogram records at our apartment, showing that epileptiform discharges in midline regions were significantly reduced either in frequency or amplitude with the improvement of ENM restricted to the lower limb and that independent epileptiform discharges in Rolandic regions from midline regions were noticed with the onset of nocturnal focal seizures. Conclusions ENM restricted to the lower limb has a close association with vertex (midline) epileptiform discharges. ENM restricted to the lower limb as the first seizure type is a peculiar phenomenon of BEVS. Some patients could evolve into BECTS or overlap with BECTS, and further into ABPE. The age of seizure onset in BEVS with ENM restricted to the lower limb as the first symptom is a little earlier than in BECTS. Ignorance of the close association between midline spikes and ENM restricted to the lower limb may lead to misdiagnosis of these patients.