Hematoporphyrin monomethyl ether mediated sonodynamic antimicrobial chemotherapy on porphyromonas gingivalis in vitro.

This study aimed to evaluate the efficacy of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic antimicrobial chemotherapy (SACT) on Porphyromonas gingivalis (P. gingivalis). P. gingivalis (ATCC 33277) was used in the present study. The bacterial suspension was randomly divided into five groups: Group 1 was incubated for 2 h in the dark with HMME in various concentrations (10, 20, 30 and 40 µg/mL). Then exposed to 1 MHz ultrasound frequency with 3 W/cm2 ultrasound intensity for 10 min. Group 2 was incubated with 40 µg/mL HMME and then irradiated with 2, 4, 6, 8 and 10 min ultrasonic time. Group 3 received different HMME concentration (10, 20, 30 and 40 µg/mL) treatment alone with no ultrasound as the HMME control group. Group 4 received ultrasound treatment alone in different ultrasonic time (2, 4, 6, 8 and 10 min) with no HMME as the ultrasound control group. Group 5 received no treatment as the no treatment control group. After the SACT, the bactericidal effect was determined by the colony forming unit assay. The intracellular content of reactive oxygen species (ROS) was detected using the laser scanning confocal microscope based on DCFH-DA. 4.7 lg reduction in CFU, When P. gingivalis was treated with ultrasound (3 W/cm2 for 10 min) at 40 µg/mL HMME concentration (P < 0.01). The intracellular ROS in SDT group had a significant difference in comparison with the no treatment control group (P < 0.01). HMME mediated SACT can be a potential antibacterial therapy to significantly inhibit P. gingivalis growth.

Nanoparticles Based on Poly (ß-Amino Ester) and HPV16-Targeting CRISPR/shRNA as Potential Drugs for HPV16-Related Cervical Malignancy.

Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (ß-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.

Severe anterior open bite with mandibular retrusion treated with multiloop edgewise archwires and microimplant anchorage complemented by genioplasty.

In this case report, we introduce the combined use of multiloop edgewise archwire and microimplant anchorage to treat an 18-year-old Chinese woman who had a severe anterior open bite and a retrusive chin. Her diagnosis included a skeletal Class II base with severe anterior open bite, backward rotated mandible, and mesially tipped buccal dentition. The treatment plan emphasized vertical control of the posterior dentoalveolar dimension. Microimplant anchors were placed in the mandibular buccal segment to provide rigid anchorage and deliver intruding forces to the posterior teeth; a multiloop edgewise archwire was applied to generate uprighting forces to the maxillary and mandibular posterior teeth. Intrusion and uprighting of the posterior teeth contributed to the counterclockwise rotation of the mandibular plane, which consequently contributed to the facial profile improvement. Orthognathic genioplasty was implemented to further improve the chin prominence. After 1.5 years of retention, ideal intercuspation was evident, and the improved facial contour was stable.

Post cross-linked ROS-responsive poly(ß-amino ester)-plasmid polyplex NPs for gene therapy of EBV-associated nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common tumors in South China and Southeast Asia and is thought to be associated with Epstein-Barr virus (EBV) infection. Downregulation of latent membrane protein 1 (LMP1) encoded by EBV can reduce the expression of NF-κB and PI3K, induce apoptosis, and inhibit the growth of EBV-related NPC. For targeted cleavage of the Lmp1 oncogene via the CRISPR/Cas9 gene editing system, a post cross-linked ROS-responsive poly(ß-amino ester) (PBAE) polymeric vector was developed for the delivery of CRISPR/Cas9 plasmids both in vitro and in vivo. After composition optimization, the resultant polymer-plasmid polyplex nanoparticles (NPs) showed a diameter of ∼230 nm and a zeta potential of 22.3 mV with good stability. Compared with the non-cross-linked system, the cross-linked NPs exhibited efficient and quick cell uptake, higher transfection efficiency in EBV-positive C666-1 cells (53.5% vs. 40.6%), more efficient gene editing ability against the Mucin2 model gene (Muc2) (17.9% vs. 15.4%) and Lmp1 (8.5% vs. 5.6%), and lower intracellular reactive oxygen species (ROS) levels. The NPs achieved good tumor penetration and tumor growth inhibition in the C666-1 xenograft tumor model via Lmp1 cleavage, indicating their potential for gene therapy of EBV-related NPC.

[Analysis of CX32 gene mutation and related clinical features in Chinese Han Charcot-Marie-Tooth families].

OBJECTIVE: To analyze the mutation of CX32 gene and related clinical features in Chinese Han patients with Charcot-Marie-Tooth (CMT) disease. METHODS: Thirty-four CMT families, from 2004 to 2011 at Departments of Neurology, Xiangya Hospital, Third Xiangya Hospital and National Key Laboratory of Medical Genetics, were selected for CX32 mutation screening after the exclusion of the PMP22 duplication and male-to-male transmission. Mutation analysis was carried out by polymerase chain reaction (PCR) plus direct sequencing. Analyses of clinical, electrophysiological and pathological features in 11 patients from 6 CMTX1 families were performed by 2 neurologists. RESULTS: Five CX32 gene mutations were detected in 6 CMT families: c.37G > A, c.65G > A, c.246C > G, c.256A > G and c.533A > G. Among them, c.246C > G and c.533A > G were firstly reported. The clinical manifestations included progressive distal muscle atrophy and weakness, areflexia, sensory abnormalities and pes vacus. Nerve conduction velocity ranged from 21.7 to 49.3 m/s. Both demyelination and axonal degeneration were detected in nerve biopsy. CONCLUSIONS: CMT1X has a frequency of around 9% in our study. The male patients tend to have more serious clinical features and their electrophysiological and pathological changes are intermediate. CX32 mutation analysis helps to confirm the genetic diagnosis of CMT so as to provide genetic counseling and reproductive guidance and elucidate its pathogenesis.

Convenient immobilization of Pt-Sn bimetallic catalysts on nitrogen-doped carbon nanotubes for direct alcohol electrocatalytic oxidation.

Pt-Sn alloy nanoparticles were conveniently immobilized on nitrogen-doped carbon nanotubes (NCNTs) through microwave-assisted ethylene glycol reduction. The nanoparticles have a narrow particle size distribution with the average particle size around 3 nm as measured by transmission electron microscopy and x-ray diffraction. The binding energy of metallic Sn passively shifts due to the charge transfer from Sn to Pt, as revealed by x-ray photoelectron spectroscopy. In comparison with the commercial Pt/C catalyst, Pt/NCNT presents a clear increase in activity for alcohol electro-oxidation due to the improved support, while the bimetallic Pt-Sn/NCNT has even higher activity owing to the alloying of Pt with Sn. Both Pt-Sn/NCNT and Pt/NCNT catalysts exhibit competitive long-term stability to Pt/C catalyst. The low cost, simple preparation and superior electrocatalytic performance indicate the great potential of Pt-Sn/NCNT in direct alcohol fuel cells.

How well do integrated 3D models predict alveolar defects after treatment with clear aligners?

OBJECTIVES: To evaluate the accuracy of integrated models (IMs) constructed by pretreatment cone-beam computed tomography (pre-CBCT) in diagnosing alveolar defects after treatment with clear aligners. MATERIALS AND METHODS: Pre-CBCT and posttreatment cone-beam computed tomography (CBCT) scans from 69 patients who completed nonextraction treatment with clear aligners were collected. The IMs comprised anterior teeth in predicted positions and alveolar bone from pre-CBCT scans. The accuracy of the IMs for identifying dehiscences or fenestrations was evaluated by comparing the means of the defect volumes, absolute mean differences, and Pearson correlation coefficients with those measured from post-CBCT scans. Defect prediction accuracy was assessed by sensitivity, specificity, positive predictive values, and negative predictive values. Factors possibly affecting changes in mandibular alveolar defects were analyzed using a mixed linear model. RESULTS: The IM measurements showed mean deviations of 2.82 ± 9.99 mm3 for fenestrations and 3.67 ± 9.93 mm3 for dehiscences. The absolute mean differences were 4.50 ± 9.35 mm3 for fenestrations and 5.17 ± 9.24 mm3 for dehiscences. The specificities of the IMs were higher than 0.8, whereas the sensitivities were both lower (fenestration = 0.41; dehiscence = 0.53). The positive predictive values were unacceptable (fenestration = 0.52; dehiscence = 0.62), and the overall reliability was low (<0.80). Molar distalization and proclination were positively correlated with significant increases in alveolar defects at the mandibular incisors after treatment. CONCLUSIONS: Alveolar defects after clear aligner treatment cannot be simulated accurately by IMs constructed from pre-CBCT. Caution should be taken in the treatment of crowding with proclination and molar distalization for the safety of alveolar bone at the mandibular incisors.

Antibacterial Activity of Polyvinyl Alcohol/WO3 Films Assisted by Near-Infrared Light and Its Application in Freshness Monitoring.

Nowadays, films with antibacterial activity and applied for freshness monitoring by colorimetric response have been drawing growing attention in food packaging. However, the development of versatile antibacterial and colorimetric agents is still highly desirable. Herein, WO3 nanorods are incorporated in a polyvinyl alcohol (PVA) matrix to develop a novel composite film with photothermal antibacterial activity and freshness monitoring faculty. The interaction between WO3 nanorods and PVA is due to hydrogen bonds. Compared with the PVA film, the presence of WO3 nanorods can significantly enhance the mechanical and barrier properties; typically, the target film (WO3/PVA)4 shows an increase in tensile strength by 52.7% and Young's modulus by 400.0% and a decrease in oxygen permeability by 72.4% and water vapor permeability by 66.9%. The films demonstrate a WO3 content-dependent antibacterial activity. Under irradiation of near-infrared light (NIR808), the synergistic effect of physical damage, oxidative stress, and temperature increase markedly improves the antibacterial activity of (WO3/PVA)4, showing an antibacterial efficiency of ∼90% against Escherichia coli or beyond 90% against Staphylococcus aureus. The incorporated WO3 nanorods demonstrate lower cytotoxicity toward the model cells of human colon cancer cell line HT-29. The (WO3/PVA)4 film exhibits colorimetric response to H2S and can also be used for pork freshness monitoring as an indicator.

pH-responsive antibacterial film based polyvinyl alcohol/poly (acrylic acid) incorporated with aminoethyl-phloretin and application to pork preservation.

This study demonstrates a pH-responsive antibacterial film based on polyvinyl alcohol/poly (acrylic acid) incorporated with aminoethyl-phloretin (PVA/PAA-AEP) for intelligent food packaging. The thermal, mechanical, barrier and light transmittance properties of PVA/PAA are enhanced by PAA presence of ≤6%. The interactions between PVA and PAA were hydrogen and ester bonds. The pH-responsive characteristic is dependent on the protonation/deprotonation tendency of the carboxylic groups on PAA in acidic/alkaline environment. The PVA/PAA3 is selected for the incorporation of AEP and its pH-responsive swelling follows Ritger-Peppas and Schott second-order models. The AEP is hydrogen bonded with the matrix of PVA/PAA3 and the release of AEP is pH-responsive and a rate-limiting step following the First-order model. With pH decrease, the predominant release control was gradually changing from polymer relaxation to Fick diffusion. The PVA/PAA3-AEP films demonstrate AEP content dependent antioxidant and antimicrobial activities. Furthermore, the antibacterial efficiency against Listeria monocytogenes and Staphylococcus aureus is significantly better than Escherichia coli. The target film PVA/PAA3-AEP3 can effectively prolong the shelf-life of pork (TVB-N < 25 mg/100 g) by 4 days at 25 °C, suggesting its great potential in intelligent food packaging.

Particle trapping using dielectrophoretically patterned carbon nanotubes.

This study presents the dielectrophoretic (DEP) assembly of multi-walled carbon nanotubes (MWCNTs) between curved microelectrodes for the purpose of trapping polystyrene microparticles within a microfluidic system. Under normal conditions, polystyrene particles exhibit negative DEP behaviour and are repelled from microelectrodes. Interestingly, the addition of MWCNTs to the system alters this situation in two ways: first, they coat the surface of particles and change their dielectric properties to exhibit positive DEP behaviour; second, the assembled MWCNTs are highly conductive and after the deposition serve as extensions to the microelectrodes. They establish an array of nanoelectrodes that initiates from the edge of microelectrodes and grow along the electric field lines. These nanoelectrodes can effectively trap the MWCNT-coated particles, since they cover a large portion of the microchannel bottom surface and also create a much stronger electric field than the primary microelectrodes as confirmed by our numerical simulations. We will show that the presence of MWCNT significantly changes performance of the system, which is investigated by trapping sample polystyrene particles with plain, COOH and goat anti-mouse IgG surfaces.

[Mutation analysis of LITAF, RAB7, LMNA and MTMR2 genes in Chinese Charcot-Marie-Tooth disease.].

The purpose of this study was to understand the mutation features of lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), ras-associated protein RAB7 (RAB7), lamin A/C (LMNA) and myotubularin-related protein 2 (MTMR2) genes in Chinese Charcot-Marie-Tooth disease (CMT) patients. Mutation analysis of LITAF gene was carried out using PCR combined with DNA sequencing, and mutation analysis of RAB7 gene by PCR-single strand conformation polymorphism (PCR-SSCP) combined with DNA sequencing in 33 CMT patients including 6 probands of autosomal domi-nated CMT families and 27 sporadic patients; mutation analysis of LMNA and MTMR2 genes was observed using PCR-SSCP combined with DNA sequencing in 41 CMT patients, including 14 probands of autosomal recessive CMT fami-lies and 27 sporadic patients. Two sequence variations c.269G-->A and c.274A-->G were detected in LITAF gene and two sequence variations c.1243G-->A and c.1910C-->T were detected in LMNA gene. No sequence variation was found in RAB7 and MTMR2 gene. Variations of c.269G-->A in LITAF gene and c.1243G-->A, c.1910C-->T in LMNA gene are newly found SNPs in this study. Variation of c.274A-->G in LITAF gene is known SNP reported in SNP database. Mutations in LITAF, RAB7, LMNA, and MTMR2 genes are rare in Chinese CMT patients.

Hyperbranched poly(ß-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer.

Persistent high-risk HPV infection is the main factor for cervical cancer. HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(ß-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(ß-amino ester) (PBAE) and plasmids were approximately 300 nm. These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice. Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.

An effective vaginal gel to deliver CRISPR/Cas9 system encapsulated in poly (ß-amino ester) nanoparticles for vaginal gene therapy.

BACKGROUND: Gene therapy has held promises for treating specific genetic diseases. However, the key to clinical application depends on effective gene delivery. METHODS: Using a large animal model, we developed two pharmaceutical formulations for gene delivery in the pigs' vagina, which were made up of poly (ß-amino ester) (PBAE)-plasmid polyplex nanoparticles (NPs) based two gel materials, modified montmorillonite (mMMT) and hectorite (HTT). FINDINGS: By conducting flow cytometry of the cervical cells, we found that PBAE-GFP-NPs-mMMT gel was more efficient than PBAE-GFP-NPs-HTT gel in delivering exogenous DNA intravaginally. Next, we designed specific CRISPR/SpCas9 sgRNAs targeting porcine endogenous retroviruses (PERVs) and evaluated the genome editing efficacy in vivo. We discovered that PERV copy number in vaginal epithelium could be significantly reduced by the local delivery of the PBAE-SpCas9/sgRNA NPs-mMMT gel. Comparable genome editing results were also obtained by high-fidelity version of SpCas9, SpCas9-HF1 and eSpCas9, in the mMMT gel. Further, we confirmed that the expression of topically delivered SpCas9 was limited to the vagina/cervix and did not diffuse to nearby organs, which was relatively safe with low toxicity. INTERPRETATION: Our data suggested that the PBAE-NPs mMMT vaginal gel is an effective preparation for local gene therapy, yielding insights into novel therapeutic approaches to sexually transmitted disease in the genital tract. FUNDING: This work was supported by the National Science and Technology Major Project of the Ministry of science and technology of China (No. 2018ZX10301402); the National Natural Science Foundation of China (81761148025, 81871473 and 81402158); Guangzhou Science and Technology Programme (No. 201704020093); National Ten Thousand Plan-Young Top Talents of China, Fundamental Research Funds for the Central Universities (17ykzd15 and 19ykyjs07); Three Big Constructions-Supercomputing Application Cultivation Projects sponsored by National Supercomputer Center In Guangzhou; the National Research FFoundation (NRF) South Africa under BRICS Multilateral Joint Call for Proposals; grant 17-54-80078 from the Russian Foundation for Basic Research.

[Mutation analysis of MFN2 gene in Chinese patients with Charcot-Marie-Tooth disease].

OBJECTIVE: To analyze MFN2 gene mutation in Chinese patients Charcot-Marie-Tooth disease (CMT) and to establish a quick and effective diagnostic method. METHODS: Through denaturing high-performance liquid chromatography (DHPLC) combined with DNA sequencing, MFN2 gene mutation analysis was carried out in 35 Chinese CMT2 patients including 9 probands of CMT2 pedigree and 26 sporadic CMT2 patients. RESULTS: The investigators found three abnormal sequence variations in MFN2 gene: c.281G-->A, c.395G-->A and c.408A-->T. c.395G-->A (C132T) was a novel causative missense mutation firstly reported while c.281G-->A (R94Q) a hotspot mutation and c.408A-->T (V136V) a single nucleotide polymorphism (SNP). The accuracy and specificity of DHPLC detection reached up to 100%. CONCLUSION: Through DHPLC combined with DNA sequencing, MFN2 mutations are detected in Chinese CMT2 patients. There are two causative missense mutations: c.395G-->A (C132T) and c.281G-->A (R94Q) and one SNP c.408A-->T (V136V). Such a method is an effective and economic diagnostic screening tool of MFN2 gene in CMT patients on a large scale.

Profiles of Human Enteroviruses Associated with Hand, Foot, and Mouth Disease in Nanjing, China.

OBJECTIVE: Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by a group of viruses. The causative viruses have changed over time, and there is a need for a more effective protective vaccine. In this study, we investigated the profiles of human enteroviruses that caused HFMD outbreaks in Nanjing in 2015, with the goal of guiding the future prevention and treatment of HFMD. METHODS: Specimens were collected from 1097 patients admitted to our hospital and diagnosed with HFMD. Enteroviruses in the specimens were identified by real-time polymerase chain reaction and epidemiological patterns were analyzed with the clinical data. RESULTS: Among the 1097 clinically diagnosed HFMD cases, 916 cases were confirmed by laboratory tests. The results showed that the main infectious virus was coxsackievirus A6 (CVA6) (41.75%), followed by enterovirus 71 (EV71) (27.48%), coxsackievirus A16 (7.43%), coxsackievirus A10 (6.84%), and others (16.51%). Further investigation indicated that CVA6 caused mild cases of HFMD, while EV71 caused severe cases. More enterovirus positive cases were reported from rural areas than from urban areas. CONCLUSIONS: CA6 and EV71 were the chief pathogenic viruses of HFMD cases in the present study. Schools, childcare centers, and families from rural areas should be the major targets for prevention and awareness of HFMD. This study will provide information useful in the prevention and management of HFMD and the development of relevant vaccines for HFMD in the future. (Disaster Med Public Health Preparedness. 2019;13:740-744).

Mandibular functional positioning only in vertical dimension contributes to condylar adaptation evidenced by concomitant expressions of L-Sox5 and type II collagen.

OBJECTIVE: Concerted expressions of L-Sox5 and type II collagen play an important part in osteogenic transition in epiphyseal cartilage. This study was designed to elucidate the role of mandibular vertical functional positioning in condylar adaptive remodelling by examining L-Sox5 and type II collagen expressions in condylar cartilage. DESIGN: 40 female Sprague-Dawley rats at age of 5 weeks were randomly divided into the experimental (n=20) and control groups (n=20). Bite plates were fitted on the upper posterior teeth of the experimental animals to induce functional repositioning of mandible in vertical dimension. The animals in both experimental and matched control groups were sacrificed on days 3, 6, 9 and 12, respectively. Tissue sections were cut in the sagittal plane through the mandibular condyles and processed with histomorphological examination for cellular response and immunohistochemical test for expressions of L-Sox5 and type II collagen. Quantitative assessment was conducted with computer-assisted imaging system to reveal the correlation between these two factors. RESULTS: (1) Both L-Sox5 and type II collagen were expressed in prechondroblastic cells and chondroblastic cells. (2) When mandible was downward positioned, the amount of L-Sox5 expression was significantly higher by 16.1% (day 9) and 24.2% (day 12) than that of the control (P<0.05); Similarly, type II collagen expression in the experimental group was also significantly stronger by 9.3% (day 9) and 12.3% (day 12) than control group (P<0.05), indicating an enhanced osteogenic transition occurring in condylar cartilage. (3) There was a similarity in temporospatial patterns between the expressions of these two factors, indicating their integral functions in facilitating condylar adaptation. CONCLUSIONS: It is suggested that L-Sox5 plays a key role in adaptive remodelling of condylar cartilage resulting from downward positioning of the mandible. Integration with type II collagen enables L-Sox5 to induce osteogenic transition and consequently to encourage endochondral ossification.

The effects of a newly designed twin-slot bracket on severely malpositioned teeth--a typodont experimental study.

The aims of this study were to design a twin-slot bracket featuring two horizontal slots and to examine its efficiency in tooth displacement. Based on the structure of a traditional edgewise bracket, an additional slot was added to a twin-slot bracket and the prototype products were fabricated for the typodont experiments. The orthodontic correction of malpositioned canines was conducted on a typodont to examine the efficiency of the twin-slot bracket in tooth displacement compared with a single-slot edgewise bracket. Three modalities of tooth movement requiring a heavy force moment, namely, axial rotation, mesiodistal tipping, and bodily translation, were conducted. The canine positions before and after simulation were measured and the changes identified. Statistical analysis was undertaken using a t-test to determine the significance of the differences in canine repositioning between the two bracket types. The results showed that in the twin-slot bracket group, the treatment changes in the canine position by derotation and uprighting were 40 +/- 3 and 25 +/- 2 degrees, respectively, compared with 20 +/- 5 and 10 +/- 2 degrees in the edgewise group (P < 0.01). When retracted into an extraction space with an initial 10 degrees of mesial tip, the mesiodistal angulation of the canines in the twin-slot bracket group remained unchanged while in the edgewise group the canines became distally tipped by 5 +/- 2 degrees (P < 0.01). The twin-slot bracket significantly increased the bracket width without reducing the interbracket span and therefore can generate increased force moments within the bracket, leading to an improved manipulation in tooth repositioning.

[A novel magnetic orthopedic appliance in treatment of preadolescent mild skeletal Class â ¢ patients].

PURPOSE: This study was to develop an intraoral Class Ⅲ orthopedic appliance using attractive magnetic forces, and investigate the effect of magnetic orthopedic appliance (MOA-Ⅲ) on skeletal and dental structures in mild skeletal Class Ⅲ children. METHODS: Thirty patients (12 boys and 18 girls) with mild skeletal Class Ⅲ jaw discrepancies were treated with MOA-Ⅲ. The average age was 9 years 3 months at the beginning of the treatment. The mean treatment period was 6.6 months. A paired t test was carried out to evaluate 40 parameters measured on cephalometric radiographs. Another 18 untreated patients (7 boys and 11 girls) according to upper criteria served as control group. SPSS15.0 software package was used for data analysis. RESULTS: The MOA-Ⅲ produced significant positive changes in maxillomandibular relationship. The maxilla was displaced anteriorly with clockwise rotation. The mandible showed slight downward and backward rotation. No significant changes were displayed in the length of the mandibular body and mandibular ramous. Significant labial tipping of the upper incisors and lingual tipping of lower incisors were noted after treatment. The measurement of soft tissues indicated that the upper lip moved forward and the lower lip retruded backward. In control group, most of the cephalometric measurements were not significantly changed except for some mandibular skeletal measurements and soft tissue measurements. CONCLUSIONS: By comparing to the untreated control, this type of magnetic orthopedic appliance is effective in the early treatment of mild skeletal Class Ⅲ malocclusion children.

Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth.

BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1 probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL, and RAB7. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics (ACMG). Clinical features were reevaluated. RESULTS: We identified three novel heterozygous variants such as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of uncertain significance. CONCLUSIONS: SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.

[Effect of functional appliance on upper airway in adolescent patients with skeletal Class II malocclusion].

PURPOSE: To investigate the effect of functional appliance on upper airway in adolescent patients with skeletal Class II malocclusion based on cone-beam CT (CBCT). METHODS: Thirty adolescent patients (male:female=1:1) with skeletal Class II malocclusion and their 30 counterparts with skeletal Class I malocclusion were selected. Skeletal Class II malocclusion patients were treated with Activator for 12 months on average, meanwhile skeletal Class I malocclusion patients were treated with fixed appliance without extraction. Cone-beam CT (CBCT) films were taken before and 12 months after treatment. Films of skeletal Class II malocclusion patients were measured (items about skeletal and upper airway, and the outline of upper airway depicted with 3D reconstruction) and compared with the reference standards and the measurements of their counterpart patients with skeletal Class I malocclusion. Independent t test was performed in inter-group comparison and paired t test was performed in inner-group comparison using SAS 8.0 software package. RESULTS: Before treatment, patients with skeletal Class II malocclusion showed decreased SNB and APDI value, increased ANB, Wits, and OJ compared with standard value and value of skeletal Class I malocclusion patients. In addition, decreased MPW and PAS value, and downsized volume of upper airway and transverse diameter minimum were found in skeletal Class II malocclusion patients. After treatment with Activator, patients with skeletal Class II malocclusion showed increased MPW and PAS value, and enlarged volume of upper airway and transverse diameter minimum. All values of skeletal items of patients with skeletal Class II malocclusion showed trends to get close to the reference standards and the values of skeletal Class I malocclusion patients. There was no significant difference between different genders of the two groups. CONCLUSIONS: Patients with skeletal Class II malocclusion have constructed upper airways. Treatment with Activator can increase the MPW and PAS values and enlarge volume of upper airway and transverse diameter minimum. Functional appliance can ameliorate the narrowness of upper airway for skeletal Class II patients.