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Background: Signal transducer and activator of transcription 3 (STAT3) was strongly expressed and activated in psoriatic keratinocytes (KCs) and correlated with the severity of psoriasis. The study aimed to investigate the effects of STAT3 small interfering RNA (siRNA) combined with ultrasonic irradiation and SonoVue microbubbles on the proliferation and apoptosis in KCs of psoriatic lesions and the relative mechanisms. Methods: Psoriatic KCs were transfected under four experimental conditions: (1) STAT3 siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group); (2) STAT3 siRNA only carried by Lipofectamine 3000 (L group); (3) the negative control of siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (siRNA-NC); (4) not treated as Blank. Cell Counting Kit-8 assay was used to evaluate the cell proliferation. Cell cycle analysis was detected with cycle test Plus DNA reagent kit associated with flow cytometer. FITC Annexin V apoptosis detection kit associated with flow cytometer was applied for apoptosis analysis. Fluo calcium indicator associated with flow cytometer was used to analyze intracellular free calcium concentration ([Ca2+]i). The expressions of cyclin D1 and Bcl-xL were detected both at the mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. The obtained data were statistically evaluated by two-way analysis of variance. Results: STAT3 siRNA inhibited the growth of KCs in a time-dependent manner showing the highest proliferation inhibition in LUS group with proliferation ratio of 45.38% ± 5.85% at 72h (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced an altered cell cycle distribution of KCs showing the highest increases in G2/M-phase population up to 18.06% ± 0.36% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced late apoptosis of KCs with the highest late apoptosis percentage of 22.87% ± 1.28% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the elevation of [Ca2+]iof KCs with the highest calcium fluorescence intensity mean of 1213.67 ± 60.51 in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the downregulation of cyclin D1 and Bcl-xL expressions of KCs at mRNA and protein levels with the lowest expressions in LUS group with cyclin D1 expression of 51.81% ± 9.58% and 70.17% ± 4.22% at mRNA level and at protein level, respectively, and with Bcl-xL expression of 37.58% ± 4.92% and 64.06% ± 7.78% at mRNA level and at protein level, respectively (P < 0.05 vs. L group, siRNA-NC, or Blank). Conclusions: STAT3 siRNA inhibited the growth and induced the apoptosis in psoriatic KCs likely partly through altering cell cycle distribution, elevating [Ca2+]i, and downregulating cyclin D1 and Bcl-xL expressions. Silencing the target gene STAT3 in psoriatic KCs with siRNA combined with ultrasonic irradiation and microbubbles would contribute to a significant innovation as a new clinical therapy for psoriasis.

Alveolar bone fenestration and dehiscence is common in untreated patients and potentially harmful. This study was to evaluate the effect of augmented corticotomy (AC) on the prevention and treatment of alveolar bone defects in skeletal class III high-angle patients during presurgical orthodontic treatment (POT). Fifty patients with skeletal Class III high-angle malocclusion were enrolled, of whom 25 patients (G1) underwent traditional POT and 25 patients (G2) received AC during POT. The alveolar bone fenestration and dehiscence around the upper and lower anterior teeth were measured by CBCT. The incidence and transition of fenestration and dehiscence in the two groups were compared by the chisquare and Mann‒Whitney rank-sum tests. Before treatment (T0), the incidence of fenestration and dehiscence around the anterior teeth of all patients was 39.24% and 24.10%, respectively. After POT (T1), the incidence of fenestration in G1 and G2 was 49.83% and 25.86%, respectively, and the incidence of dehiscence in G1 and G2 was 58.08% and 32.07%, respectively. For teeth without fenestration and dehiscence at T0, more anterior teeth in G1 exhibited fenestration and dehiscence at T1 than in G2. For teeth with fenestration and dehiscence at T0, most transitions in G1 were maintained or worsened, but "cure" cases were observed in G2. After POT, the cure rates of fenestration and dehiscence in G2 were 80.95% and 91.07%, respectively. During the POT of skeletal Class III high-angle patients, augmented corticotomy can significantly treat and prevent alveolar bone fenestration and dehiscence around anterior teeth. [ABSTRACT FROM AUTHOR]

As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular matrix (ECM) in the periodontal ligament (PDL). The ECM of the PDL consists of various types of collagens and other glycoproteins. The specific process and mechanism of ECM remodelling during orthodontic tooth movement remains unclear. Collagen I and III, which constitute major components of the PDL, are upregulated under orthodontic force. The changes in the contents of ECM proteins also depend on the expression of ECM-related enzymes, which organise new collagen fibre networks to adapt to changes in tooth position. The matrix metalloproteinase family is the main enzyme that participates in collagen hydrolysis and renewal and changes its expression under orthodontic force. Moreover, ECM adhesion molecules, such as integrins, are also regulated by orthodontic force and participate in the dynamic reaction of cell adhesion and separation with the ECM. This article reviews the changes in ECM components, related enzymes and adhesion molecules in the PDL under orthodontic force to lay the foundation for the exploration of the regulatory mechanism of ECM remodelling during orthodontic tooth movement.

Objective: To explore the high-efficiency and low-risk prevention and treatment strategies for stem cells from human exfoliated deciduous teeth (SHED) for high-altitude cerebral oedema., Methods: A low-pressure and low-oxygen tank mimicking high-altitude conditions was used to establish the high-altitude cerebral oedema animal model. The preventive effects of SHED for cerebral oedema were then evaluated by haematoxylin and eosin (H&E) and histological staining. In vitro, SHED was co-cultured with BV-2 to analyse the effects of SHED by western blot and immunofluorescence staining., Results: SHED can prevent and treat cerebral oedema in a high altitude rat animal model. Mechanistically, SHED treatment can protect brain cells from apoptosis induced by high altitude condition. Moreover, SHED treatment can inhibit M1-type polarisation and promote M2-type polarisation of microglia cells via the suppression of hypoxia inducible factor (HIF)- 1α-mediated extracellular signal-regulated kinase (ERK) signalling activated in high altitude condition., Conclusion: SHED treatment can relieve high-altitude cerebral oedema via inhibiting HIF- 1α-mediated ERK signalling, which indicates that SHED is a promising alternative strategy to prevent and treat high-altitude cerebral oedema.

Objective: To analyse the effects of premolar extraction on the upper airway in adult and adolescent orthodontic patients using CBCT., Methods: The Embase, Web of Science, Cochrane Library and Medline (via PubMed) databases were searched with no language restrictions. Longitudinal studies in which CBCT was applied to assess the effects of tooth extraction on the upper airway were included in the analysis. Two authors performed the study selection, methodological quality assessment, data extraction and data synthesis independently., Results: A total of 12 studies were included, six of which were eligible for quantitative synthesis. In the adult group, the nasopharynx and oropharynx volume showed no significant change, and the minimum cross-sectional area of the upper airway demonstrated a non-significant decrease compared to the non-extraction group. In the adolescent group, the nasopharynx volume, oropharynx volume and minimum cross-sectional area of the upper airway increased in a non-significant manner., Conclusion: The currently available evidence indicates that tooth extraction does not increase the risk of airway collapse in adult and adolescent patients. The present findings should be interpreted with caution and evaluated in further high-quality studies.

In this case study, we report the successful treatment of a 35-year-old woman with a hyperdivergent skeletal pattern, open bite and severe transverse deficiency, exhibiting a skeletal Class III malocclusion. The treatment plan included 3D correction of these issues with surgically assisted rapid maxillary expansion (SARME) to solve the transverse deficiency, presurgical orthodontic treatment including aligning and levelling of the teeth in both arches, LeFort I osteotomy and bilateral sagittal split ramus osteotomy, and postsurgical correction of malocclusion. Orthodontic treatment was performed with labial brackets, and the patient achieved satisfactory occlusion and a significantly improved facial profile. Retention at the 1-year follow-up showed stable occlusion and arch forms with a harmonious facial profile.

In our previous studies, we have shown that (D-Ser2) oxyntomodulin (Oxm), a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide, protects hippocampal neurons against Aβ 1-42 -induced cytotoxicity, and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons. Additionally, we have demonstrated that (D-Ser2) Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer's disease model mice. However, the protective mechanism remains unclear. In this study, we showed that 2 weeks of intraperitoneal administration of (D-Ser2) Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer's disease model mice. In addition, electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that (D-Ser2) Oxm increased the power of the theta rhythm. In addition, (D-Ser2) Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer's disease model mice. These findings suggest that (D-Ser2) Oxm improves the cognitive function of Alzheimer's disease transgenic mice by recovering hippocampal synaptic function and theta rhythm., Competing Interests: None

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid β (Aβ) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aβ deposition and the excessive activation of microglia in the hippocampus.

Background: Cleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 (RUNX2). Here, we report a sporadic Chinese case presenting typical symptoms of CCD., Methods: We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 frameshift mutation: c.1111dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2., Results: RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated., Conclusions: We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes., Competing Interests: There are no conflicts of interest.

Purpose: To compare the treatment effects in patients with maxillary protrusion between implant anchorage and traditional intraoral anchorage., Methods: Thirty patients with maxillary protrusion treated with bilateral maxillary first premolars extractions and high anchorage were selected. They were randomly divided into implant anchorage group and traditional intraoral anchorage group. Each group had 15 cases. The casts and the cephalograms were obtained before treatment (T1) and after treatment (T2). Three-dimensional model analysis was used to compare the teeth movements between the two groups and cephalometric analysis was used to compare the changes of skeletal and soft tissues. The differences were analyzed with SPSS 17.0 software package., Results: In the implant anchorage group, the upper central incisors were retracted by (6.661±1.328) mm and intruded by (0.129±1.815) mm. In the traditional intraoral anchorage group, the upper central incisors were retracted by (5.788±2.009) mm and extruded by (2.623±1.776) mm. There was no significant difference between the two groups in sagittal movement (P>0.05), but there was significant difference in vertical movement (P<0.05). In the implant anchorage group, the upper first molars were protracted by (0.608±1.045) mm, intruded by (0.608±1.045) mm and moved palatally by (0.477±0.904) mm. In the traditional intraoral anchorage group, the upper first molars were protracted by (1.503±0.945) mm, extruded by (0.072±0.690) mm and moved palatally by (0.883±0.752)mm. There was significant difference between the two groups in sagittal movement and vertical movement (P<0.05), but there was no significant difference in horizontal movement(P>0.05). There was no significant difference between the two groups in the changes of cephalometric measurements of skeletal and soft tissues (P>0.05)., Conclusions: Implant anchorage may be superior in vertical control of the maxillary incisors and also superior in sagittal and vertical control of the maxillary molars to traditional intraoral anchorage during management of maxillary protrusion.

Objective: To investigate the clinical features of invasive fungal disease (IFD) in children without underlying diseases., Methods: The clinical data of 49 children without underlying diseases who were diagnosed with IFD were retrospectively studied., Results: Fungal pathogens were detected in 37 (76%) out of 49 patients, including Cryptococcus neoformans (17 children, 46%), Candida albicans (10 children, 27%), Aspergillus (3 children, 8%), and Candida parapsilosis (3 children, 8%). Fungal pneumonia (17 children, 46%) was the most commonly seen disease, with Candida albicans as the major pathogen (9 children, 53%). The 49 children had at least one high-risk factor for infection, including the use of antibiotics, a long length of hospital stay, and invasive procedures. Of all the children, 82% did not respond well to antibiotic treatment or experienced recurrent pyrexia. Among the 24 children who underwent G tests, 17 (71%) showed positive results. All the children were given antifungal therapy, and among these children, 37 (75%)were cured, 3 (6%) were still in the treatment, 5 (10%) died, and 4 (8%) were lost to follow-up., Conclusions: In IFD children without underlying diseases, Cryptococcus neoformans and Candida are the main pathogens, and lung infection is the most common disease. Long-term use of high-dose antibiotics may be an important risk factor for fungal infection. The IFD children without underlying diseases are sensitive to antifungal drugs and have a satisfactory prognosis.

Objective: To correlate the objective cephalometric measurements with subjective facial esthetics in patients with bimaxillary protrusion., Materials and Methods: The sample consisted of 60 Asian-Chinese patients with bimaxillary protrusion who met the inclusion criteria. The facial esthetics of posttreatment profile and the change of profile on standardized lateral photographs were rated by a panel of 10 orthodontists and a panel of 10 lay persons with bimaxillary protrusion. All of the pretreatment and posttreatment cephalograms were digitized and traced. Twenty-five cephalometric measurements were constructed and analyzed. Correlations between the subjective facial esthetic scores and each cephalometric measurement were evaluated., Results: The cephalometric measurements correlated with the facial esthetic scores of posttreatment profile given by the orthodontist and the lay persons were basically the same. For the evaluation of posttreatment profile in bimaxillary protrusion patients, the upper and lower lip to E-line, upper and lower incisor tip to AP plane, Pg-NB distance, mentolabial angle, and sulcus depth correlated significantly with the esthetic score. For the evaluation of profile change during orthodontic treatment, retraction of upper incisor relative to AP plane or the perpendicular line through sella (line Y), change of upper incisor inclination, change of mentolabial sulcus depth, and retraction of lips relative to E-line were correlated positively with the esthetic value., Conclusions: Cephalometric measurements of lip position, incisor position, and chin morphology were key parameters correlated to facial esthetics.

Objective: To investigate the alveolar bone defects of anterior alveolar bone in patients with bimaxillary protrusion by using cone-beam computed tomography (CBCT)., Methods: The samples consisted of 50 patients with bimaxillary protrusion, who were assigned to the teenage group[20 cases, (13.1±1.0) years] and adult group[30 cases, (22.9±4.2) years]. The adult group included 9 hypo-divergent, 11 normo-divergent and 10 hyper-divergent patients. The images were obtained by using NewTom VG CBCT and the alveolar defects were evaluated., Results: The ratio of the patients had alveolar bone defects was 94.00%. Meanwhile, the defects were associated with 38.60% of all the teeth. Most defects occurred on labial alveolar bone (98.66%); fenestration was found more in the maxillary alveolar region and dehiscence occurred more in the mandible. The dehiscences (3.06%) and defects prevalence (30.13%) of the teenage group were significant lower than those of the adult group (11.73% vs. 42.46%), P<0.05; while there was no significance of the fenestrations prevalence between the two group (P>0.05). The hypo-divergent group had lower fenestrations prevalence (22.22%) than the normo-divergent (33.84%) and hyper-divergent groups (37.50%), P<0.05. The upper central incisor had the lowest alveolar bone defect prevalence., Conclusion: Alveolar bone defects are common findings in patients with bimaxillary protrusion before orthodontic treatment. The prevalence of defects is affected by age and vertical-growth type.