Masticatory function in growing individuals with hypohidrotic ectodermal dysplasia: A longitudinal study.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder with agenesis of ectodermal derivatives, causing oligodontia or anodontia. Dentures are needed to improve the patients' mastication. AIM: This study aimed at preliminarily evaluating the masticatory function changes in Chinese individuals with HED after prosthetic rehabilitation from childhood to adolescence. DESIGN: This longitudinal study enrolled 10 HED patients. Data were collected during childhood and adolescence, respectively. The healthy children and adolescents were recruited as the control group. The surface electromyography (EMG) of masseter (MM) and anterior temporalis (TA) muscles during clenching and chewing were recorded. The EMG activity, asymmetry index (As), activity index (Ac), and chewing cycle were analyzed. The masticatory efficiency was measured by spectrophotometry with subjective masticatory ability assessed by a questionnaire. RESULTS: The EMG activities and masticatory efficiency of HED patients during childhood and adolescence were mostly lower with a higher As (p < .05). The chewing process enhanced the TA activity and balanced the As of HED adolescents (p > .05). The HED adolescents showed a more prevalent TA activity (p < .05). CONCLUSION: The masticatory function of the growing HED patients was functionally inferior to the dentate individuals with a narrowed gap from childhood to adolescence.

Biomechanically based Fu's subcutaneous needling treatment for senile knee osteoarthritis: protocol for a randomized controlled trial.

INTRODUCTION: Fu's subcutaneous needling (FSN) is a new type of acupuncture that uses subcutaneous tissue to oscillate from side to side to improve muscle pathology status and can be effective in treating Knee osteoarthritis. Nonetheless, whether the clinical effect is similar to that of most commonly used drugs is unclear. Thus, this study aims to determine the pain-relieving effect and improvement in the joint function of the FSN therapy by comparing it with that of a positive control drug (celecoxib). Furthermore, this clinical trial also aims to evaluate the effect of FSN on gait and lower limb muscle flexibility, which can further explore the scientific mechanisms of the FSN therapy. METHODS AND ANALYSIS: This study is a randomized, parallel-controlled, single-center prospective clinical study that includes 60 participants, with an FSN group (n = 30) and a drug group (n = 30). The Fu's subcutaneous needling (FSN) group undergo the FSN therapy 3 times a week for 2 weeks, while the drug group receives 0.2 g/day oral celecoxib for 2 weeks, with a follow-up period of 4 weeks after the completion of treatment. The primary outcome is the difference in the visual analog scale score after 2 weeks of treatment compared with baseline. The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, joint active range of motion test, three-dimensional gait analysis, and shear wave elastic imaging technology analysis in lower limb muscles are also performed to demonstrate clinical efficacy. ETHICS AND DISSEMINATION: The trial is performed following the Declaration of Helsinki. The study protocol and consent form have been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine. All patients will give informed consent before participation and the trial is initiated after approval. The results of this trial will be disseminated through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06328153.

A novel mutation in the collagen domain of EDA results in hypohidrotic ectodermal dysplasia by impacting the receptor-binding capability.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) mainly results from gene mutations in the EDA/EDAR/NF-κB pathway. Function analysis of the mutations in the collagen domain of ectodysplasin A (EDA)result in HED has been rarely studied. This study aimed at determining the mechanism by which the novel collagen domain mutation of EDA results in HED. METHODS: We analyzed the DNAs from a Chinese family with HED and performed bioinformatics analysis. A new three-dimensional structure model of the EDA trimer was built and used to predict the effect of the mutations on EDA. We performed a western blot to detect EDA1 proteins in cell lysates and supernatants. We then performed coimmunoprecipitation to determine whether the mutation would affect the interaction of EDA1 with the EDA receptor (EDAR). Dual luciferase reporter assay and immunofluorescence were performed to detect the effect of the mutant EDA1 protein on nuclear factor kappa B (NF-κB) activation. RESULTS: A novel missense mutation (c.593G > A, p. Gly198Glu) in the collagen domain of EDA was detected. The mutation was predicted to be disease-causing. A three-dimensional structure model of the EDA trimer was first built in this study, in which the mutation site is located around the receptor binding domain. Functional studies showed that there was no difference in the secretion activity between the mutant EDA1 and the wild-type EDA1. However, the receptor-binding activity and the transcription activation of NF-κB were impaired by the mutation. CONCLUSION: We identified a novel mutation (c.593G > A, p. Gly198Glu) in the collagen domain of EDA. Bioinformatics analysis and functional studies showed this mutation was damaging, indicating that mutations in the collagen domain of EDA could result in HED by affecting the receptor-binding activity of EDA and the transcriptional activity of NF-κB.

Discovery of N-benzylarylamide derivatives as novel tubulin polymerization inhibitors capable of activating the Hippo pathway.

Novel N-benzylarylamide saderivatives were designed and synthesized, and their antiproliferative activities were explored. Some of 51 target compounds exhibited potent inhibitory activities against MGC-803, HCT-116 and KYSE450 cells with IC50 values in two-digit nanomolar. Compound I-33 (MY-875) displayed the most potent antiproliferative activities against MGC-803, HCT-116 and KYSE450 cells (IC50 = 0.027, 0.055 and 0.067 µM, respectively) and possessed IC50 values ranging from 0.025 to 0.094 µM against other 11 cancer cell lines. Further mechanism studies indicated that compound I-33 (MY-875) inhibited tubulin polymerization (IC50 = 0.92 µM) by targeting the colchicine bingding site of tubulin. Compound I-33 (MY-875) disrupted the construction of the microtubule networks and affected the mitosis in MGC-803 and SGC-7901 cells. In addition, although it acted as a colchicine binding site inhibitor, compound I-33 (MY-875) also activated the Hippo pathway to promote the phosphorylation status of MST and LATS, resulting in the YAP degradation in MGC-803 and SGC-7901 cells. Due to the degradation of YAP, the expression levels of TAZ and Axl decreased. Because of the dual actions on colchicine binding site and Hippo pathway, compound I-33 (MY-875) dose-dependently inhibited cell colony formatting ability, arrested cells at the G2/M phase and induced cells apoptosis in MGC-803 and SGC-7901 cells. Moreover, compound I-33 (MY-875) could regulate the levels of cell cycle and apoptosis regulatory proteins in MGC-803 and SGC-7901 cells. Furthermore, molecular docking analysis suggested that the hydrogen bond and hydrophobic interactions made compound I-33 (MY-875) well bind into the colchicine binding site of tubulin. Collectively, compound I-33 (MY-875) is a novel anti-gastric cancer agent and deserves to be further investigated for cancer therapy by targeting the colchicine binding site of tubulin and activating the Hippo pathway.

A risk prediction model for dysphagia in older patients: a single-center prospective study.

Surveys based on western populations have identified many risk factors for dysphagia in older people, but the potential risk factors consistent with the demographic characteristics of older, hospitalized Chinese patients require further study. This single-center prospective study aimed to determine the incidence of dysphagia in western China, and to develop and validate a model to predict the risk of dysphagia among older patients. A total of 343 inpatients (aged ≥ 65 years without dysphagia and cognitive impairment) were included. A score ≥ 2 on the Eating Assessment Tool-10 was defined as dysphagia. After a six-month follow-up, 70 (20.4%) patients were found to have dysphagia. The final model included age, wearing dentures, activities of daily living, cerebral vascular disease, coronary heart disease, and malignancy. The developed model has high predictive accuracy and can be easily implemented in daily practice.

Impairment mechanism of nasal mucosa after radiotherapy for nasopharyngeal carcinoma.

The nasal mucosa, which performs the crucial functions of filtering, humidifying and temperature regulation, is one of the most vulnerable areas of nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). Following RT, NPC patients experience a series of pathological changes in the nasal mucosa, ultimately leading to physiological dysfunction of the nasal epithelium. This article systematically reviews the clinical and pathological manifestations of RT-related nasal damage in NPC patients and summarizes the potential mechanism of damage to the human nasal epithelium by RT. Finally, we outline the current mechanistic models of nasal epithelial alterations after RT in NPC patients and provide additional information to extend the in-depth study on the impairment mechanisms of the nasal mucosa resulting from RT. We also describe the relationship between structural and functional alterations in the nasal mucosa after RT to help mitigate and treat this damage and provide insights informing future clinical and fundamental investigations.

Facial Morphological Changes Following Denture Treatment in Children with Hypohidrotic Ectodermal Dysplasia.

Purpose: The purpose of this study was to characterize the facial morphology of Chinese children with hypohidrotic ectodermal dysplasia (HED) and quantify facial changes after prosthetic treatment. Methods: 3-D facial images of 12 HED children were taken and their facial morphology was compared against 28 healthy controls. Facial changes due to denture placement were also quantified. Group differences were quantified and visualized by superimposing the average faces with robust Procrustes superimposition. Partial least square regression was used to investigate the effects of group membership (HED or controls, pre- and posttreatment) on facial morphology. Results: HED patients had a more prominent forehead, depressed nasal region, depressed zygomatic zone, flat cheeks, and protuberant lips and chin compared with controls. The strongest differences were localized in the middle and lower face, especially in the cheeks and zygomatic and chin regions (P<0.05). Pre- and post-treatment comparisons showed the chin retruded (P<0.05). Statistical facial differences between the posttreatment patients and the controls were localized in the perinasal area and submental region (P<0.05). Conclusions: The facial morphology of Chinese children with hypohidrotic ectodermal dysplasia differs significantly from healthy children, creating a more concave facial profile. Posttreatment facial changes provide a better understanding of dentures' role in improving facial appearance.

A novel missense mutation p.S305R of EDA gene causes XLHED in a Chinese family.

X-linked hypohidrotic ectodermal dysplasia (XLHED) can be characterized by hypohidrosis, sparse hair, hypodontia, and characteristic facial features and is usually caused by mutations of ectodysplasin A (EDA) gene located on the X chromosome. In this study, we examined a HED pedigree and studied the molecular genetics of the disease. A novel missense mutation was revealed by direct sequencing analysis in the EDA exon 7 (c.913 A > C, p.S305R). The impact of the mutation on the protein was studied in vitro in human embryonic kidney 293 T cells transfected with mutant or wild type forms of EDA. The mutant-type EDA1 protein showed impaired solubility comparing with wild-type EDA1. This novel missense EDA mutation was considered to be the cause of HED in the pedigree reported here. Our findings, combined with those reported elsewhere, provide an improved understanding of the pathogenic mechanism of HED as well as important information for a genetic diagnosis.

INPP5D rs35349669 polymorphism with late-onset Alzheimer's disease: A replication study and meta-analysis.

Inositol polyphosphate-5-phosphatase (INPP5D) was reported to be associated with Alzheimer's disease (AD) through modulating the inflammatory process and immune response. A recent genome-wide association study discovered a new locus single nucleotide polymorphism (SNP, rs35349669) of INPP5D which was significantly associated with susceptibility to late-onset Alzheimer's disease (LOAD) in Caucasians. In this study, we investigated the relations between the INPP5D polymorphism rs35349669 and LOAD in Han Chinese population comprising 984 LOAD cases and 1352 healthy controls being matched for age and gender. Our results showed no obvious differences in the genotypic or allelic distributions of rs35349669 polymorphism between LOAD cases and healthy controls (genotype: p = 0.167; allele: p = 0.094). Additionally, when these data were stratified by APOEε4 status, there are still no evident differences in the genotypic or allelic distributions in APOEε4 carriers (p > 0.05). Furthermore, meta-analysis of 81964 individuals confirmed that rs35349669 was significantly associated with the risk for LOAD (OR=1.08, 95%CI=1.06-1.11), but the results remained negative in Chinese subgroup (OR=0.77, 95%CI=0.53-1.13). Overall, the current evidence did not indicate that INPP5D rs35349669 polymorphism play a role in the genetic predisposition to LOAD in Chinese population.

[Masticatory performance and assessment of life quality of children with ectodermal dysplasia after prosthetic rehabilitation].

OBJECTIVE: To evaluate masticatory performance and life quality of children with ectodermal dysplasia (ED) after prosthetic rehabilitation. METHODS: Six children with ED received denture restoration and 18 healthy children were involved in this study. The surface electromyography (EMG) of masseter (MM) and anterior temporalis (TA) during clenching and chewing movement were recorded. The EMG amplitude, area, asymmetry index of total and activity index of MM/TA were compared at each stage. The masticatory efficiency was measured with spectrophotometer. The life quality was assessed using visual analogue scale questionnaire. RESULTS: The EMG amplitude of MM and TA during chewing in ED Group were 41.7% and 45.6% of the control group respectively, the area were 35.9% and 36.0% respectively. Significant difference in asymmetry index of total during clenching was observed between the two groups (P < 0.05) but not during chewing (P > 0.05). The differences of activity index of MM/TA during clenching and chewing between the two groups were not detected (P > 0.05). The masticatory efficiency of ED group was 67.2% of the control group. The score of chewing function in children with ED after prosthetic rehabilitation was three times higher than before, and no difference was present between the two groups (P > 0.05). CONCLUSIONS: Early prosthetic rehabilitation can significantly improve the masticatory performance and life quality of children with ED.

Tooth abnormalities in congenital infiltrating lipomatosis of the face.

OBJECTIVE: The aim of this study was to present a literature review and case series report of tooth abnormalities in congenital infiltrating lipomatosis of the face (CIL-F). METHODS: Four typical cases of CIL-F are presented. Tooth abnormalities in CIL-F documented in the English literature are also reviewed. The clinical and radiological features of tooth abnormalities are summarized. RESULTS: In total, 21 cases with tooth abnormalities in CIL-F were retrieved for analysis. Accelerated tooth formation and eruption (17 cases), macrodontia (9 cases), and root hypoplasia (8 cases) were observed in CIL-F. CONCLUSION: Tooth abnormalities including accelerated tooth formation or eruption, macrodontia, and root hypoplasia are common in CIL-F.

Mutational analysis of RUNX2 gene in Chinese patients with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor-encoding gene, RUNX2. To correlate different RUNX2 mutations with CCD clinical spectrum, we studied six independent Chinese CCD patients. In five patients, mutations were detected in the coding region of the RUNX2 gene, including two frameshift mutations and three missense mutations. Of these mutations, four were novel and one had previously been reported. All the detected mutations were exclusively clustered within the Runt domain that affected conserved residues in the Runt domain. In vitro green fluorescent protein fusion studies showed that the three mutations--R225L, 214fs and 172fs--interfered with nuclear accumulation of RUNX2 protein, while T200I mutation had no effect on the subcellular distribution of RUNX2. There was no marked phenotypic difference between patients in craniofacial and clavicles features, while the expressivity of supernumerary teeth in our patient cohort had a striking variation, even among family members. The occurrence of intrafamilial clinical variability raises the view that hypomorphic effects and genetic modifiers may alter the clinical expressivity of these mutations. Our results provide new genetic evidence that mutations involved in RUNX2 contribute to CCD.