Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.

In Vitro Evaluation of the Antibacterial Properties of Tea Tree Oil on Planktonic and Biofilm-Forming Streptococcus mutans.

Streptococcus mutans (S. mutans) is the principal etiologic agent in the occurrence of human dental caries and the formation of biofilms on the surface of teeth. Tea tree oil (TTO) has been demonstrated to exhibit a wide range of pharmacological actions that can effectively inhibit the activity of bacteria. In this context, we evaluated the in vitro antimicrobial effects of TTO on S. mutans both during planktonic growth and in biofilms compared with 0.2% CHX. We determined the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using the microdilution method, the bacteriostatic rate using an MTT assay, and the antimicrobial time using a time-kill assay. Then, we explored the effects of TTO on acid production and cell integrity. Furthermore, the effects of TTO on the biomass and bacterial activity of S. mutans biofilms were studied. Finally, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to investigate the structure and activity of biofilms. The MIC and MBC values were 0.125% and 0.25%, and the bacterial inhibition rate was concentration dependent. TTO can effectively inhibit bacterial acid production and destroy the integrity of the cell membrane. Electron micrographs revealed a reduction in bacterial aggregation, inhibited biofilm formation, and reduced biofilm thickness. The effect of TTO was the same as that of 0.2% CHX at a specific concentration. In summary, we suggest that TTO is a potential anticariogenic agent that can be used against S. mutans.

Autotransplantation of mature impacted tooth to a fresh molar socket using a 3D replica and guided bone regeneration: two years retrospective case series.

BACKGROUND: The aim of this study was to evaluate the clinical outcome of autotransplantation of mature third molars to fresh molar extraction sockets using 3D replicas. METHODS: Ten patients underwent teeth autotransplantation with or without GBR. We observed the mobility, percussion, radiography examination, the probing depth and the masticatory function of the transplanted teeth during 2 years following up, which were transplanted into fresh molar sockets by using 3D replicas, and GBR when it is necessary. RESULTS: The average extra-oral time of donor tooth had been shortened to 1.65 min when used the 3D replica. Some probing depth of the transplanted tooth were deeper than 3 mm at 4 or 5 weeks temporarily. And one patient felt slight sensitive when chewing with soft food at 4 weeks, then disappeared. The clinical examination of the autotransplantation teeth during 1 year follow-up showed no sign of failure. CONCLUSIONS: The tooth autotransplantation using 3D replica with or without GBR is an effective method which can reduce the extra-oral time of the donor teeth and may result in less failure.

Saliva and Plasma Monohydroxycarbamazepine Concentrations in Pediatric Patients With Epilepsy.

BACKGROUND: Monohydroxycarbamazepine (MHD, 10-hydroxy-carbamazepine) is the main active metabolite of oxcarbazepine (OXC). The present study aims to investigate the relationship between plasma and saliva concentrations of MHD in Chinese children with epilepsy. METHODS: Plasma and saliva samples were collected and MHD levels were measured by high-performance liquid chromatography system. Linear regression analysis was conducted between the dose of OXC and saliva concentrations, between the dose of OXC and plasma concentrations, and between the saliva concentrations and plasma concentrations. Student's t-test was used for unpaired data. A one-way analysis of variance was used for analyzing co-medication in subgroups of patients. RESULTS: A total of 58 blood samples and 58 saliva samples were obtained from 52 pediatric epileptic patients, with a median age of 5.67 years (0.58-15 years, 23 males and 29 females). There was an apparent positive correlation between the plasma and saliva MHD concentrations [Y = 0.77x - 0.85 (n = 58), R = 0.908, P < 0.01]. MHD plasma and saliva concentrations were positively correlated to daily drug dose (r = 0.461 and 0.417; P < 0.01 respectively). The saliva/plasma MHD ratio was around 0.71 and had no significant difference with age, gender, and combined medications. When data were analyzed for subgroups (one group taking OXC as monotherapy, the second group taking OXC in add-on with non-enzyme-inducing antiepileptic drugs, and the third group taking OXC in add-on with hepatic-enzyme-inducing antiepileptic drugs or moderate inducers), no significant difference was found between plasma and saliva MHD concentrations in all the above 3 groups. CONCLUSIONS: High correlation between plasma and saliva MHD levels supported the use of saliva as an alternative to plasma for OXC monitoring in children with epilepsy.

Regulating inflammation and apoptosis: A smart microgel gene delivery system for repairing degenerative nucleus pulposus.

The progression of intervertebral disc degeneration (IDD) is attributed to the gradual exacerbation of cellular apoptosis and impaired extracellular matrix (ECM) synthesis, both of which are induced by progressive inflammation. Therefore, it is crucial to address the inflammatory microenvironment and rectify the excessive apoptosis of nucleus pulposus cells (NPCs) to achieve intervertebral disc (IVD) regeneration. In this study, we devised a smart microgel gene delivery system that incorporates functionalized gene nanoparticles (NPs) for the purpose of IVD regeneration. siGrem1 was loaded into the NPs to enhance their antiapoptotic ability and protective effects. Furthermore, the encapsulation of HADA further endows the NPs (referred to as HSGN) with targeted delivery and anti-inflammatory effects, as well as reactive oxygen species (ROS) scavenging capacities. To create an microenvironment-responsive microgel system, phenylboronic acid-functionalized microspheres (referred to as M.S.) were fabricated and dynamically loaded with the HSGN. This microgel system (MHSGN), which is highly biocompatible, enables the sustained release of siGrem1, effectively modulating inflammation, scavenging ROS, and alleviating apoptosis in NPCs. These multifunctional capabilities promote the restoration of metabolic homeostasis within the nucleus pulposus ECM, ultimately leading to delayed IDD.

A 3-year follow-up clinical study on the preservation for vitality of involved tooth in jaw cysts through an innovative method.

Jaw cysts commonly affect the oral and maxillofacial region, involving adjacent tooth roots. The management of these teeth, particularly regarding root canal therapy and apicoectomy, lacks consensus. This study introduces a novel treatment concept and refined surgical approach to preserve pulp viability in teeth involved in jaw cysts. The objective was to investigate the effectiveness and potential benefits of this approach over a 36-month follow-up period. A conservative management approach prioritized vitality preservation, reserving root canal treatment and apicectomy for cases with post-operative discomfort. A comprehensive follow-up of 108 involved teeth from 36 jaw cyst cases treated with the modified method was conducted. Clinical observation, X-ray imaging, cone-beam computed tomography (CBCT), and pulp vitality testing assessed changes in cyst size, tooth color, pulp vitality, root structure, and surrounding alveolar bone. After 36 months, our modified surgical approach successfully preserved tooth vitality in 84 involved teeth. Adverse symptoms in 19 teeth, such as redness, swelling, fistula, and pain, resolved with postoperative root canal therapy. Follow-up was lost for five teeth in two cases. No cyst recurrences were observed, and in 34 cases, the bone cavity gradually disappeared, restoring normal bone density during long-term follow-up. Our modified surgical method effectively preserves tooth vitality in jaw cysts. This innovative approach has the potential to improve the management of teeth involved in jaw cysts.

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy.

Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been extensively investigated for self-assembly. They are widely applied owing to their desirable biocompatibility, biodegradability, and tunable architecture. The development of peptide-based nanoparticles often requires complex synthetic processes involving chemical modification and supramolecular self-assembly. Stimuli-responsive peptide nanoparticles, also termed "smart" nanoparticles, capable of conformational and chemical changes in response to stimuli, have emerged as a class of promising materials. These smart nanoparticles find a diverse range of biomedical applications, including drug delivery, diagnostics, and biosensors. Stimuli-responsive systems include external stimuli (such as light, temperature, ultrasound, and magnetic fields) and internal stimuli (such as pH, redox environment, salt concentration, and biomarkers), facilitating the generation of a library of self-assembled biomaterials for biomedical imaging and therapy. Thus, in this review, we mainly focus on peptide-based nanoparticles built by self-assembly strategy and systematically discuss their mechanisms in response to various stimuli. Furthermore, we summarize the diverse range of biomedical applications of peptide-based nanomaterials, including diagnosis and therapy, to demonstrate their potential for medical translation.

[Clinical and cone-beam CT analysis of 368 patients with temporomandibular joint disc perforation in different age groups].

PURPOSE: The aim of this study was to investigate the clinical characteristics of disc perforation (DP) of temporomandibular joint (TMJ) at different ages. METHODS：Patients with TMJ disc perforation admitted to the Department of Trauma and Temporomandibular Joint Surgery Stomatological Hospital of Wuhan University, from April 2012 to May 2021 were included in this study. They were divided into 6 groups according to different ages. Clinical and CBCT radiographic features were analyzed. Clinical features included maximal interincisal opening, pain, clicking，and occlusal changes. Imaging features included condylar absorption flattening, hyperplasia or osteophyte formation, sclerosis, subchondral cysts, depression defects, and blurred anterior slope. The clinical and imaging characteristics of patients in different age groups were statistically analyzed. SPSS 26.0 software was used for statistical analysis, and Chi-square test was used to compare the distribution of clinical symptoms and imaging features in patients of different ages. RESULTS: A total of 368 patients were collected, including 24 males, with an average age of 27.63±15.90 years. There were 344 females with an average age of 32.61±15.61 years. The incidence of pain was 21.31%, occlusal change was 50.82%, and condylar absorption flat was 50.82% in the 10-19 age group. The incidence of pain in 20-29 age group was 31.06%, occlusal change was 53.42%, and condylar absorption flattening was 45.34%. In 50-59 age group, the incidence of pain was 83.33%, occlusal changes were 2.38%, and hyperplasia or osteophyte formation was 47.62%. In age group ≥60 years old, the incidence of pain was 82.86%, occlusal changes were 2.86%, and hyperplasia or osteophyte formation was 60%. CONCLUSIONS: In terms of clinical features, patients under 40 years old are more likely to have occlusal changes, while patients over 40 years old are most likely to have joint pain. Radiographically, patients under 40 years old are mainly characterized by bone loss in the condyle, while patients over 40 years old are mainly characterized by condylar hyperplasia.

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer.

Rationale: Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically. Methods: Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties. Results: We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both in vitro and in vivo, which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens. Conclusion: Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).

Inflammation-Responsive Drug-Loaded Hydrogels with Sequential Hemostasis, Antibacterial, and Anti-Inflammatory Behavior for Chronically Infected Diabetic Wound Treatment.

Stimuli-responsive hydrogels possess unique advantages in drug delivery due to their variable performance and status based on the external environment. In the present study, a dual-responsive (pH and reactive oxygen species (ROS)) hydrogel was prepared to realize drug release properties under inflammatory stimulation. By grafting 3-carboxy-phenylboronic acid to the gelatin molecular backbone and cross-linking with poly(vinyl alcohol), we successfully synthesized the inflammation-responsive drug-loaded hydrogels after encapsulation with vancomycin-conjugated silver nanoclusters (VAN-AgNCs) and pH-sensitive micelles loaded with nimesulide (NIM). This novel design not only retained the dynamic functions of hydrogels, such as injectability, self-healing, and remodeling, but also realized sequential and on-demand drug delivery at diabetic-infected wound sites. In this work, we found that the hydrogel exhibited excellent biocompatibility and hemostasis properties owing to the enhanced cell-adhesive property of the gelatin component. The significant antibacterial and anti-inflammatory effect of the hydrogel was demonstrated in an in vitro experiment. Moreover, in the in vivo experiment, the hydrogel was found to play a role in promoting infected wound healing through sequential hemostasis and antibacterial and anti-inflammatory processes. Collectively, this inflammation-responsive hydrogel design containing VAN-AgNCs and NIM-loaded micelles has great potential in the application of chronically infected diabetic wound treatment, as well as in other inflammatory diseases.

Biomechanical and Morphometric Evaluation of a Strontium-Incorporated Implant and Four Commercially Available Implants: A Study in Rabbits.

PURPOSE: Strontium has shown a positive effect on osseointegration in experiments. This study compared surface characterization and osseointegration of a strontium-incorporated implant with four commercial implants with different surface treatments. MATERIALS AND METHODS: A strontium-oxide layer was created by hydrothermal treatment on the surface of the implant (SLA-Sr). Surface characterizations were observed using a scanning electron microscope, three-dimensional (3D) optical microscope, and x-ray energy-dispersive spectrometry. Implants of different surface treatments including resorbable blasting media (RBM), sandblasting with large grit and acid etching (SLA-1, SLA-2), sandblasting and thermal acid etching (STA), and SLA-Sr were implanted into the proximal tibiae and femoral condyles of rabbits. Biologic effects were evaluated by removal torque testing and histomorphometric analysis after 3, 6, and 12 weeks of implantation. RESULTS: Nanostructures were observed on the surface of SLA-Sr and STA. Calcium (Ca) was detected on the surface of RBM. Sr was detected on the surface of SLA-Sr. SLA-1 and STA had greater surface roughness than SLA-2, SLA-Sr, and RBM (P < .05). In vivo, SLA-Sr achieved better removal torque value (RTV) than that of RBM and SLA-2 at 3 weeks (P < .05), as well as increased bone area ratio (BA%) in cortical bone compared with RBM at 3 weeks (P < .05). STA showed higher bone-to-implant contact ratio (BIC%) in cortical bone than RBM at 3 and 6 weeks (P < .05). Compared with RBM, SLA-1 had better RTV at 6 weeks and higher BIC% in cortical bone at 12 weeks (P < .05). CONCLUSION: In vivo, compared with SLA-2 and RBM, the implant with the strontium-oxide layer displayed slight advantages in new bone formation and osseointegration in the early healing stage. In the later osseointegration stage, the results of SLA-Sr were comparable with other implants.

[Application of computer virtual design to assist the accuracy of socket preparation during tooth autotransplantation].

PURPOSE: It was aimed to apply computer virtual design and digital surgical templates to simulate postoperative position of tooth and guide the accuracy of socket preparation during tooth autotransplantation. METHODS: The study enrolled 10 patients who underwent tooth autotransplant surgery. Cone-bean CT (CBCT) data were imported into Proplan CMF 3.0 software. The donor tooth was transferred to the recipient site according to the occlusion and space situation. A digital template was designed to guide socket preparation. Computer-aided rapid prototyping (RP) technique was used to print the surgical template and tooth model. RESULTS: With computer virtual design and digital template, it was possible to accurately guide socket preparation in recipient site. The six-month follow-up results showed the periodontal space in the radiographs was continuous and intact. There was no mobility in all cases and the probing depth of the tooth was <4 mm. The related data showed a favorable survival and success rates of the donor teeth. CONCLUSIONS: Computer virtual design can successfully simulate postoperative position in tooth autotransplantation while simplifying the surgical procedure, and enhance the accuracy of socket preparation.

Endoscopic near-infrared dental imaging with indocyanine green: a pilot study.

Current dental diagnosis, especially tooth abnormalities, relies largely on X-ray-based imaging, a technique that requires specialized skills and suffers from ionizing radiation. Here, we present a pilot study in rats of an efficient, ionizing-radiation-free and easy-to-use alternative for dental imaging. Postnatal rats at different ages were injected with indocyanine green and molars were imaged by a laboratory-designed endoscopic near-infrared (NIR) dental imaging system. The results indicate that the endoscopic NIR dental imaging can be used to observe the morphology of postnatal rat molars, especially at early postnatal stages when morphology of the molar is indistinguishable under visible conditions. A small abnormal cusp was observed and distinguished from the normal cusps by the NIR dental imaging system. Dental structures, such as unerupted molars, can be imaged as soon as 10 min after the injection of indocyanine green; imaging after 24 h shows improved imaging contrast. Overall, the endoscopic NIR fluorescence dental imaging system described here may be useful in dental research; this technique may serve as a safe, real-time imaging tool for dental diagnosis and treatment beyond experimental systems in the future.

[Evaluation of using Proplan virtual software in teaching of orthognathic surgery].

PURPOSE: Using Proplan virtual software to construct a virtual teaching platform for orthognathic surgery, and to explore an effective teaching model for orthognathic surgery. METHODS: One-hundred grade four students of stomatology in Fujian Medical University were divided into two groups. Traditional orthognathic surgery teaching method and Proplan virtual software teaching method were employed to teach the two groups of students, respectively. Orthognathic-surgery-related paper test was used to evaluate how the two groups of students understand orthognathic surgery; then the students were switched to the other teaching method, respectively. A follow-up questionnaire survey was conducted to further evaluate students' acceptance of the two teaching methods. Finally, a comprehensive statistical analysis was performed for students understanding of orthognathic surgery using SPSS 11.0 software package. RESULTS: According to the test scores, students in the experimental group scored higher than the control group, the difference was significant (P<0.01). The acceptance of different teaching methods displayed remarkable difference between the two groups. Token together, our finding showed that virtual model surgery teaching was an easier teaching method for students to understand and accept. CONCLUSIONS: Proplan virtual software teaching improves the teaching efficiency of orthognathic surgery and deserves further promotion.

[Clinical effect of modified alveolar cleft repair with bone grafting].

PURPOSE: To evaluate the clinical effect of improved alveolar cleft repair with bone grafting. METHODS: Forty one cases with alveolar cleft treated by modified operation between 2008-2016 were included. The modified techniques were as follow: incision design, preparation of bone graft bed, bone removal and bone grafting, etc. The therapeutic effect was analyzed. RESULTS: The successful rate was 92.8%. After 6-12 months of follow-up, bone graft survived well with no obvious complications. CONCLUSIONS: Iliac bone is a good source for bone graft. Improvement of tight tension-free suture in bone bed is the key to surgical success.

Type II Odontoid Fracture with Atlantoaxial Dislocation Presenting as Symptomatic Seizures: A Case Report.

OBJECTIVE AND BACKGROUND: To report symptomatic seizures of a patient with an old type II odontoid fracture with atlantoaxial dislocation. The type II odontoid fracture is a dangerous disease and presents as neurological deficits. Because of the compression of upper cervical cord, without timely diagnosis and treatment, a type II odontoid fracture may result in sudden death. Although it has been shown that epileptic seizures may lead to type II odontoid fracture, there is no report of symptomatic seizures in patients with odontoid fracture. METHODS: A 16-year-old adolescent boy with neurological deficits, especially grand mal seizures for duration of 5 years, was diagnosed as an old type II odontoid fracture with atlantoaxial dislocation and treated in our hospital. A 1-year follow-up was performed. RESULTS: Systematic analyses of the clinical history, manifestations, physical examination, and radiologic results of the patient revealed an old type II odontoid fracture. Magnetic resonance imaging showed spinal cord compression and degeneration. The patient received posterior atlantoaxial fixation and fusion procedure following successful closed reduction. The frequency of seizures was reduced to once a month and there was a thorough recovery in other neurological functions 1 year after the operation. CONCLUSIONS: Old type II odontoid fracture might present as symptomatic seizures in addition to other neurological deficits. Posterior atlantoaxial screw-plate fixation and fusion is an effective treatment for old type II odontoid fracture.

Fabrication of metal-organic framework MIL-88B films on stainless steel fibers for solid-phase microextraction of polychlorinated biphenyls.

Metal-organic frameworks (MOFs) have received considerable attention as novel sorbents for sample preparation due to their fascinating structures and functionalities such as large surface area, good thermal stability, and uniform structured nanoscale cavities. Here, we report the application of a thermal and solvent stable MOF MIL-88B with nanosized bipyramidal cages and large surface area for solid-phase microextraction (SPME) of polychlorinated biphenyls (PCBs). Novel MIL-88B coated fiber was fabricated via an in situ hydrothermal growth of MIL-88B film on etched stainless steel fiber. The MIL-88B coated fiber gave large enhancement factors (757-2243), low detection limits (0.45-1.32ngL(-1)), and good linearity (5-200ngL(-1)) for PCBs. The relative standard deviation (RSD) for six replicate extractions of PCBs at 100ngL(-1) on MIL-88B coated fiber ranged from 4.2% to 8.7%. The recoveries for spiked PCBs (10ngL(-1)) in water and soil samples were in the range of 79.7-103.2%. Besides, the MIL-88B coated fiber was stable enough for 150 extraction cycles without significant loss of extraction efficiency. The developed method was successfully applied to the determination of PCBs in water samples and soil samples.

[Episodic central nervous system symptoms with reversible white matter involvement in Chinese patients with X-linked Charcot-Marie-Tooth disease and literatures review].

OBJECTIVE: To analyze the phenotype and genotype of CMTX1 patients with episodic transient reversible white matter involvement, and delineate the features of brain MRI in the episode and the possible mechanisms. METHOD: Three Chinese probands and their family members were sequenced in the coding regions of GJB1. With the other 16 reported CMTX1 patients with episodic transient reversible white matter involvement, the clinical feature of the episodic central nervous system symptoms and the genotypes were reviewed. RESULT: Missense mutations in GJB1 were identified in all 3 probands. In 19 patients with transient reversible white matter involvement, the episodes were manifested as weakness of the limbs, dysarthria, and dysphagia, without disturbance of consciousness or seizures. The episodes lasted for 13 hours (10 min-72 hours) with complete remission in all patients; There were multiple episodes in 9 patients. During the episode, brain MRI showed symmetrical high signals in T2 weighted, Flair and DWI images in periventricular white matter, with predominance in posterior region including splenium of corpus callosum. These changes in imaging were most prominent during or within 1 week after the clinical episode.Significant improvements occurred within 1 month, with complete remission within 4-6 months.No specific locations of mutant amino acids in GJB1 protein were found in these patients with episodic transient reversible white matter involvement. CONCLUSION: Episodic transient reversible white matter involvement may present in a small number of patients with CMTX1. Transient edema of oligodendrocytes due to the dysfunction of gap junction may be involved in the pathogenesis. There is no correlation between the location of the mutant amino acids in GJB1 and the occurrence of the episodes.