Circular RNA CircACAP2 regulates temporomandibular joint osteoarthritis via miR-21-5p/PLAG1 axis.

OBJECTIVES: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR-21-5p may participate in the TMJOA development and the interaction between circRNA-ACAP2 (CircACAP2) and miR-21-5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. MATERIALS AND METHODS: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR-21-5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual-luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. RESULTS: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR-21-5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. CONCLUSIONS: The present study unveiled that CircACAP2/miR-21-5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA.

Does the Lingual-Based Mucoperiosteal Flap Reduce Postoperative Morbidity Compared With the Buccal-Based Mucoperiosteal Flap After the Surgical Removal of Impacted Third Molars? A Meta-analysis Review.

PURPOSE: The lingual-based mucoperiosteal flap, a novel flap, was unclear about the effects on the prognosis of surgery for impacted mandibular third molars. This study aimed to compare the lingual- and buccal-based mucoperiosteal flaps with respect to postoperative responses and complications. MATERIALS AND METHODS: A systematic review with a meta-analysis was designed and the PubMed, Cochrane Library, EMBASE, and Web of Science databases and Google Scholar from January 1, 2000 to April 30, 2020 were searched for randomized clinical trials. The predictor variable was buccal- or lingual-based flap in the surgery, and the outcome variables were pain, swelling, trismus, operative time, and wound dehiscence. Other study variables were sex and retention depth of impacted teeth. RevMan 5.3 software was used for data analysis. Mean differences or standardized mean differences and risk ratios were computed to assess associations between 2 variables, where statistical significance was set at P < .05. RESULTS: Seven publications met the inclusion criteria, contributing 370 subjects who had 590 teeth removed to sample. The lingual-based flap failed to significantly reduce postoperative discomfort. However, subgroup analysis revealed that subjects who underwent comma flap (a type of lingual-based flap) surgeries complained of milder pain than those who underwent buccal-based flap surgeries on day 1 (mean difference = -1.18, 95% confidence interval [CI] [-1.53, -0.83], P < .001) and day 7 (mean difference = -1.80, 95% CI [-2.13, -1.48], P < .001) after surgery. Significant differences were also observed on days 1, 3, and 7 regarding postoperative swelling and trismus (P < .01). In addition, the lingual-based flap was reported to cause a significantly lower rate of wound dehiscence (relative risk = 0.46, 95% CI [0.30, 0.69], P = .0002). CONCLUSIONS: The lingual-based flap was associated with better primary wound closure in third molar removal. The comma flap, as a subtype, was preferable for relieving postoperative pain, swelling, and trismus over the buccal-based flap.

Clinicopathologic study on a rare variant of ameloblastoma with basal cell features.

OBJECTIVES: To investigate the clinical features, pathologic manifestations, and biologic behaviors of a variant of ameloblastoma with basal cell features (AM-BC). MATERIALS AND METHODS: Following retrospective review of the clinical and pathological data of six cases of AM-BC, we described their histological and immunohistochemical (IHC) features and discussed the biologic behaviors, prognoses, pathogenesis, and clinical relevance of AM-BC. Direct sequencing of polymerase chain reaction products was also performed in all cases. RESULTS: The six cases of AM-BC involved four women and two men, aged 22-82 years. Four lesions occurred in the maxilla and two in the mandible. Histologically, the basal cells tended to be arranged as unequally sized follicles, strands, or cords of odontogenic epithelium in the connective tissue stroma. Little or no stellate reticulum was present in the central portion of the nest. Expression of CKs was consistent with other histological variants of ameloblastoma (AM), but AM-BC had significantly higher p53 and Ki-67 (p < 0.05) labeling indices than other histological variants of AM. Two patients had BRAF gene mutations. CONCLUSION: Ameloblastoma with basal cell features is a very rare variant of AM. Our study showed the differences and relationships that exist between AM-BC and other variants of AM, which could enhance understanding of AM-BC.

Oral Bromelain for the Control of Facial Swelling, Trismus, and Pain After Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study was to evaluate whether bromelain can decrease trismus, pain, and facial swelling in patients undergoing impacted third molar surgery. MATERIALS AND METHODS: Three databases were searched to identify relevant studies through November 1, 2017. Randomized controlled trials (RCTs) that compared the effect of bromelain versus placebo after mandibular third molar surgery were included. The main outcome measures, pain, facial swelling, and trismus, were assessed in the early stage (2 to 3 days) and the late stage (7 days) after surgery. Standardized mean differences (SMDs) and weighted mean differences (WMDs) were calculated using fixed-effect models. All statistical analyses were implemented using Review Manager 5.3. RESULT: Six RCTs were included in this meta-analysis. The pooled results suggested that bromelain appears to be effective for decreasing facial swelling in the early and late stages after surgery (early-stage SMD, -0.24; 95% confidence interval [CI], -0.46 to -0.02; P = .03; late-stage SMD, -0.54; 95% CI, -0.84 to -0.24; P = .0004). Bromelain alleviated postoperative pain 7 days after surgery (SMD, -0.54; 95% CI, -0.87 to -0.20; P = .002), but there was no significant difference in pain levels at the early stage. For trismus, analyses showed that bromelain had no apparent effect on early or late trismus. CONCLUSION: Bromelain conferred moderate relief of postoperative discomfort after third molar surgery.

Anesthetic Efficiency of Articaine Versus Lidocaine in the Extraction of Lower Third Molars: A Meta-Analysis and Systematic Review.

PURPOSE: The purpose of this study was to evaluate whether the anesthetic efficiency of articaine is superior to that of lidocaine during lower third molar extraction (LTME). MATERIALS AND METHODS: Three electronic databases (PubMed, Cochrane, and Web of Science) were searched to identify randomized controlled trials up to December, 31 2017. Five evaluation indexes were extracted, namely success rate of anesthesia, subjective onset time of anesthesia, objective onset time of anesthesia, duration time of anesthesia, and intraoperative pain assessment, to assess the anesthesia efficiency of the 2 solutions. All data analyses were conducted using Review Manager (version 5.3; The Cochrane Collaboration, London, United Kingdom). RESULTS: Nine studies were included in this review. The sample was composed of 770 LTMEs from 493 patients, with 382 LTMEs in the lidocaine group and 388 LTMEs in the articaine group. Compared with lidocaine, 4% articaine with 1:100,000 epinephrine showed a higher success rate of anesthesia (risk ratio, 1.10; 95% confidence interval [CI], 1.01 to 1.21; P = .03), shorter subjective onset time of anesthesia (standardized mean difference, 1.20; 95% CI, 0.50 to 1.89; P = .0007), and longer duration time of anesthesia (mean difference, 0.83 hours; 95% CI, 0.59 to 1.07 hours; P < .00001); however, for intraoperative pain assessment (mean difference, 3.12 mm; 95% CI, -0.13 to 6.37 mm; P = .06) and objective onset time of anesthesia (standardized mean difference, 0.44; 95% CI, -0.39 to 1.26; P = .30), there was no significant difference between the 2 solutions. CONCLUSIONS: The results of this study suggest that 4% articaine with 1:100,000 epinephrine possesses superior anesthetic efficiency relative to lidocaine for inferior alveolar nerve blocks during LTME.

Effectiveness of Drainage in Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study was to provide an evidence-based evaluation of the impact of surgical drainage after the removal of mandibular third molars. MATERIALS AND METHODS: The Medline (PubMed), Cochrane Library, and Web of Science databases were searched to identify randomized controlled trials up to September 1, 2017. Postoperative variables, including facial swelling, trismus, and pain, were calculated early (2 to 3 days) and late (5 to 7 days) after the removal of impacted mandibular third molars. Weighted mean differences for trismus and standardized mean differences (SMDs) for swelling and pain were pooled for the included studies. RESULTS: The samples consisted of 592 extractions (297 with surgical drainage and 295 controls) in 409 participants. The included studies were published from 1988 to 2016. Participants who received surgical drainage had significantly less facial swelling during the early stage (SMD, -0.46; 95% confidence interval [CI], -0.67 to -0.26; P < .0001) and the late stage (SMD, -0.36; 95% CI, -0.55 to -0.16; P = .0004) after the removal of an impacted mandibular third molar. They also had better mouth opening than controls during the early and late stages (early MD, 5.55 mm; 95% CI, 2.31-8.79; P = .0008; late MD, 2.38 mm; 95% CI, 1.47-3.29; P < .0001). The level of pain was significantly different between the 2 groups in the early stage (SMD, -0.55; 95% CI, -1.00 to -0.10; P = .01); however, there were no significant differences in the late stage (SMD, -0.13; 95% CI, -0.38 to 0.12; P = .30). CONCLUSION: The use of surgical drainage has an obviously positive effect on postoperative reactions after the removal of a mandibular third molar. Given the need for additional time for clinic visits, surgical drainage presents an alternative for the perioperative management of impacted mandibular third molar surgery, especially in cases of a fully bony tooth with poor drainage.

Epidemiology and Prognostic Factors Analysis of Electrical Injuries in Shaanxi, China: A Single-Center Observational Study of 385 Cases.

The objective of this research is to investigate the epidemiological features of electrical injuries in Shaanxi Province, China, examine their prognosis, and ascertain the factors that impact the outcomes. Telephone follow-ups were conducted with electrical injury patients at our hospital between 2011 and 2021, yielding the following results: Most electrical injuries occur in males (94.3%) and younger or middle-aged individuals. The most common voltages involved are 220V and 380V. Since 2016, there has been a 20.1% annual decrease in electrical injuries, with most cases occurring from April to September. Patients typically undergo 1 surgical procedure (0,3), with a 14.8% amputation rate and an average hospital stay of 21 days (9,43). 1.8% of electrical injury patients have died, 17.1% have permanent nerve damage, and 10.8% need help with daily tasks. 18.5% have psychological issues and 9.6% have PTSD. 93.7% return to work in an average of 6 months (2,12). Amputation risk is influenced by voltage, muscle injury, and current pathway; skin grafting risk is mainly due to voltage. Heart injuries are affected by unconsciousness and current pathways; labor loss risk factors include voltage, falls from heights, and muscle injury; nerve damage is linked to muscle injury. Cataract development risk is associated with electric shock to the head and neck. It is crucial to address the psychological well-being of patients and provide necessary support. Patient input should be taken into account when deciding on treatment for non-functional limbs. Physicians should evaluate prognostic factors and provide appropriate treatment to enhance patient outcomes.

[Imaging characteristic of Stafne bone cavity：a retrospective study based on cone-beam CT].

PURPOSE: To guide clinical decision-making more efficiently via collecting and analyzing the imaging data of patients with Stafne bone cavity(SBC). METHODS: Six patients with SBC were retrospectively reviewed in Stomatological Hospital of Shandong University. By assessing cone-beam CT (CBCT) data, age, sex, complaint, cavity location, diameter at three dimension, maximal cross-sectional area of multi-planar reconstruction planes, content gray scale, morphological classification and its relationship with mandibular canal were recorded respectively. RESULTS: A total of 6 cases were inadvertently found on CBCT, with no symptoms. The locations of SBC were between mandibular molar region and mandibular angle, inferior border of mandible and mandibular canal, mostly at lingual side. Three were on the left and three were on the right. The bone cavity was elliptic and its long axis was consistent with the long axis of the mandible, with an average long axis diameter of (16.43±4.54) mm, horizontal axis diameter of (6.91±1.48) mm, vertical axis diameter of (10.24±2.10) mm. According to the multi-planar reconstruction planes readings, the maximal cross-sectional area of the bone cavity was (91.93±25.52) mm2, the maximal coronal area was (57.26±23.23) mm2, and the maximal sagittal area was (127.80±51.22) mm2. In view of the classification in the relationship between SBC marginal line and buccal cortical bone, there were 2 cases of type I cavity, 3 cases of type II cavity and 1 case of type III cavity. The connection between the bone cavity and the surrounding anatomical structure was classified into 3 conditions: covering penetration, adjacency and separation on the basis of the relative position between the cavity boundary with the mandibular inferior margin and the mandibular canal in sagittal plane. In addition, the content type could be primarily identified depending on estimation of corrected grey scale in the center of bone cavity. CONCLUSIONS: CBCT can make an intuitive and clear diagnosis of Stafne bone cavity, which brings great significance into the early clinical decision-making, thus not only avoiding unnecessary surgery, reducing the waste of additional medical resources, but also decreasing the physical and mental trauma of patients.

Corrigendum: Circadian rhythm protein Bmal1 modulates cartilage gene expression in temporomandibular joint osteoarthritis via the MAPK/ERK pathway.

[This corrects the article DOI: 10.3389/fphar.2020.527744.].

Potential targets identified in adenoid cystic carcinoma point out new directions for further research.

Adenoid cystic carcinoma (AdCC) of the head and neck originates from salivary glands, with high risks of recurrence and metastasis that account for the poor prognosis of patients. The purpose of this research was to identify key genes related to AdCC for further investigation of their diagnostic and prognostic significance. In our study, the AdCC sample datasets GSE36820, GSE59702 and GSE88804 from the Gene Expression Omnibus (GEO) database were used to explore the abnormal coexpression of genes in AdCC compared with their expression in normal tissue. A total of 115 DEGs were obtained by screening with GEO2R and FunRich software. According to functional annotation analysis using Enrichr, these DEGs were mainly enriched in the SOX2, AR, SMAD and MAPK signaling pathways. A protein-protein network of the DEGs was established by the Search Tool for the Retrieval of Interacting Genes (STRING) and annotated through the WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and was shown to be enriched with proteins involved in cardiac muscle cell proliferation and extracellular matrix organization. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that ITGA9, LAMB1 and BAMBI were associated with the PI3K-Akt and TGF-ß pathways. Furthermore, 36 potential target miRNAs were identified by the OncomiR and miRNA Pathway Dictionary Database (miRPathDB). In conclusion, SLC22A3, FOXP2, Cdc42EP3, COL27A1, DUSP1 and HSPB8 played critical roles according to the enrichment analysis; ITGA9, LAMB1 and BAMBI were involved in significant pathways according to the KEGG analysis; ST3Gal4 is a pivotal component of the PPI network of all the DEGs obtained; SPARC, COL4A2 and PRELP were highly related to multiple malignancies in pan-cancer research; hsa-miR-29-3p, hsa-miR-132-3p and hsa-miR-708-5p were potential regulators in AdCC. The involved pathways, biological processes and miRNAs have been shown to play significant roles in the genesis, growth, invasion and metastasis of AdCC. In this study, these identified DEGs were considered to have a potential influence on AdCC but have not been studied in this disease. The analysis results promote our understanding of the molecular mechanisms and biological processes of AdCC, which might be useful for targeted therapy or diagnosis.

Periostin Mediates Condylar Resorption via the NF-κB-ADAMTS5 Pathway.

Although the up-regulation of periostin in osteoarthritic (OA) is found, its function on OA condyle caused by disc displacement is not clear. Our objective was to explore whether periostin has any effect on condylar resorption. We initially identified periostin-positive cells in temporomandibular joint osteoarthritic (TMJ-OA) cartilage. Furthermore, the vitro analysis confirmed that the expression of periostin in chondrocytes treated with a static pressure of 150 kpa and 200 kpa for 3 h by an in-house-designed pressure chamber. To explore the underlying mechanism, we found that periostin can induce IκBα phosphorylation and its subsequent degradation, leading to consequent p65 nuclear translocation and subsequent induction of ADAMTS5 expression, which is known to be detrimental to cartilage extracellular matrix production. Importantly, inhibiting NF-κB signaling, by BAY 11-7082 treatment, rescued periostin-induced ADAMTS5 up-regulation. This study elucidated the direct role of periostin in condylar resorption, which was found to occur via NF-κB-ADAMTS5 signaling. Inhibition of this pathway might provide a new strategy for TMJ-OA treatment.

CircRNA_ACAP2 Suppresses EMT in Head and Neck Squamous Cell Carcinoma by Targeting the miR-21-5p/STAT3 Signaling Axis.

Circular RNAs (circRNAs) contain microRNA (miRNA)-specific binding sites and can function as miRNA sponges to regulate gene expression by suppressing the inhibitory effect of miRNAs on their target genes. MiR-21-5p has been reported to be involved in the development of head and neck squamous cell carcinoma (HNSCC) and plays an important role in the activation of epithelial-mesenchymal transition (EMT). However, the upstream regulatory mechanism and downstream targets of miR-21-5p in tumor cells remain unknown. CircRNA_ACAP2 inhibits the function of miR-21-5p by binding to its specific binding sites in HNSCC cells. Overexpression of CircRNA_ACAP2 inhibits the proliferation and migration of HNSCC cells, while downregulation of CircRNA_ACAP2 has the opposite effect. STAT3 is a direct target gene of miR-21-5p and a transcription factor of ZEB1. We demonstrate that CircRNA_ACAP2 functions as a tumor suppressor gene in HNSCC and that its function is regulated via the miR-21-5p/STAT3 signaling axis.

Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis.

AIMS: The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). METHODS: TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR. RESULTS: UAC altered the histological structure and extracellular matrix content of cartilage in the temporomandibular joint (TMJ), and KO of MiR21 alleviated this effect (p < 0.05). Upregulation of MiR21 influenced the expression of TMJ-OA related molecules in mandibular condylar chondrocytes via targeting Gdf5 (p < 0.05). Gdf5 overexpression significantly decreased matrix metalloproteinase 13 (MMP13) expression (p < 0.05) and reversed the effects of MiR21 (p < 0.05). CONCLUSION: MiR21, which acts as a critical regulator of Gdf5 in chondrocytes, regulates TMJ-OA related molecules and is involved in cartilage matrix degradation, contributing to the progression of TMJ-OA. Cite this article: Bone Joint Res 2020;9(10):689-700.

DAPT inhibits titanium particle-induced osteolysis by suppressing the RANKL/Notch2 signaling pathway.

Artificial prosthesis is wildly used in clinical medicine for degenerative disease such as osteoclast-related diseases. However, the material wear particles released from the surface of prostheses cause prosthetic loosening as a result of aseptic osteolysis in long-term use. Therefore, it is important to find an agent that inhibits the formation and function of osteoclast for therapeutic use. Notch signaling pathway plays a lot of roles in cell proliferation, differentiation, and apoptosis. However, the role of Notch signaling pathway in osteoclastogenesis remains unclear. The aim of this study is to assess the effects of γ-secretase inhibitor DAPT on osteoclastogenesis via Notch signaling pathway in vitro and titanium particle-induced osteolysis in vivo. In animal experiments, the inhibitory effect of DAPT on titanium particle-induced osteolysis in a mouse calvaria model was demonstrated. Interestingly, few resorption pits were observed following administration of DAPT and almost no osteoclasts formed at high concentration of DAPT. in vitro experiments revealed the mechanism of the effects of DAPT on osteoclastogenesis. DAPT inhibited the formation and function of osteoclast by blocking RANKL-induced Notch2-NF-κB complex signaling pathway. In conclusion, these results indicated that DAPT could prevent and cure titanium particle-induced prosthetic loosening and other osteoclast-related diseases.

MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1.

BACKGROUND: Due to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1. METHODS: TMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue (TB), immunohistochemical (IHC) staining, Western blotting (WB) and RT-qPCR. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. WB, RT-qPCR, IHC and TB were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo chorioallantoic membrane (CAM) assay and WB. RESULTS: In the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged, and miR-21-5p and UAC model were shown to affect the expression of Spry1, IL-1ß, MMP-13, and VEGF. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1ß, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway. CONCLUSION: This study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway.

The purpose of this study was to elucidate the role of the circadian gene Bmal1 in human cartilage and its crosstalk with the MAPK/ERK signaling pathway in temporomandibular joint osteoarthritis (TMJ-OA). We verified the periodical variation of the circadian gene Bmal1 and then established a modified multiple platform method (MMPM) to induce circadian rhythm disturbance leading to TMJ-OA. IL-6, p-ERK, and Bmal1 mRNA and protein expression levels were assessed by real-time RT-PCR and immunohistochemistry. Chondrocytes were treated with an ERK inhibitor (U0126), siRNA and plasmid targeting Bmal1 under IL-6 simulation; then, the cells were subjected to Western blotting to analyze the relationship between Bmal1 and the MAPK/ERK pathway. We found that sleep rhythm disturbance can downregulate the circadian gene BMAL-1 and improve phosphorylated ERK (p-ERK) and IL-6 levels. Furthermore, Bmal1 siRNA transfection was sufficient to improve the p-ERK level and aggravate OA-like gene expression changes under IL-6 stimulation. Bmal1 overexpression relieved the alterations induced by IL-6, which was consistent with the effect of U0126 (an ERK inhibitor). However, we also found that BMAL1 upregulation can decrease ERK phosphorylation, whereas ERK downregulation did not change BMAL1 expression. Collectively, this study provides new insight into the regulatory mechanism that links chondrocyte BMAL1 to cartilage maintenance and repair in TMJ-OA via the MAPK/ERK pathway and suggests that circadian rhythm disruption is a risk factor for TMJ-OA.

Safety and sedative effect of intranasal dexmedetomidine in mandibular third molar surgery: a systematic review and meta-analysis.

OBJECTIVE: The focus of this meta-analysis was to assess the sedative effect and safety of intranasal dexmedetomidine (Dex) in mandibular third molar surgery. METHODS: The PubMed/Medline, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases were searched for studies published until May 1, 2018. Eligible studies were restricted to randomized controlled trials (RCTs) and controlled clinical trials. The evaluation indicators mainly included the bispectral index, observer assessment of alertness/sedation scale, systolic blood pressure, and heart rate. Data for each period in the Dex and control groups were pooled to evaluate its sedative effect and safety. RESULTS: Five RCTs met the inclusion criteria. This study included 363 patients: 158 patients received intranasal inhalation of Dex before surgery, and 158 patients were negative controls. The pooled results showed a good sedative effect during tooth extraction when intranasal inhalation of Dex was performed 30 minutes before third molar extraction (assessment of alertness/sedation, Dex vs control SMD -1.20, 95% CI -1.73 to -0.67, I 2=0, P=0.95; bispectral index, Dex vs control SMD -11.68, 95% CI -19.49 to -3.87, I 2=89%; P=0.0001), and parameters returned to normal within 90 minutes after inhalation. During the operation, blood pressure and heart rate decreased to some extent, but the decreases did not exceed 20% of the baseline, and all patients returned to normal conditions within 90 minutes after inhalation. CONCLUSION: Intranasal inhalation of Dex 30 minutes before third molar extraction can provide a good sedative effect, and large-sample multicenter RCTs are needed to evaluate the analgesic effect of Dex.

Comprehensive assessment of tranexamic acid during orthognathic surgery: A systematic review and meta-analysis of randomized, controlled trials.

The objective of this study was to comprehensively assess the use of tranexamic acid (TXA) during orthognathic surgery. A systematic review and meta-analysis of randomized controlled trials addressing these issues were carried out. Three electronic databases, included PubMed, Web of Science, and Cochrane Library, were searched until April 30, 2018. Eligible studies were restricted to randomized, controlled trials (RCTs). Weighted mean differences (WMD) for blood loss, operation time, haematocrit, quality of surgical field, and odds ratio (OR) for transfusion rates were pooled for the included studies. Eight randomized, controlled trials were included for analysis. Compared with the control group, the TXA group showed a reduction in intraoperative blood loss of 165.03 ml (p < 0.00001; 95% CI, -200.93 to -129.13 ml), a reduction in the drop of haematocrit of 2.32 g/dl (p < 0.00001; 95% CI, -3.38 to -1.26 g/dl), and an improved quality of surgical field (p < 0.00001; MD, -1.01; 95% CI, -1.23 to -0.80). Tranexamic acid has a limited effect on reducing operative time (p < 0.00001; MD, -16.18 min; 95% CI, -19.60 to -12.75 min) and on decreasing the transfusion rates (p = 0.02; OR = 0.33; 95% CI, 0.13 to 0.83).

HIF-1-VEGF-Notch mediates angiogenesis in temporomandibular joint osteoarthritis.

Angiogenesis has been reported participated in temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis is unclear, recent studies indicate that hypoxia is important in TMJ-OA. In order to induce osteoarthritis-like lesions in mandibular condyles, rats were sleep deprived experimentally. An increased number of blood vessels were observed in the rats' condyles of SD and SR group compared with controls. Protein and mRNA levels of related factors including VEGF, HIF-1 and Notch were investigated by means of immunohistochemical staining, western blot and real-time PCR, which were highly expressed in the TMJ-OA rats. Furthermore, Cell test was designed to study effects of hypoxia on condylar chondrocytes. We found the expression of VEGF, HIF-1 and Notch were significantly increased in hypoxia group, indicating that HIF-1-Notch-VEGF signaling pathway were activated by hypoxia. The inhibitors of HIF-1 and Notch could suppress the expression of HIF-1, VEGF, Notch, suggesting the HIF-1-VEGF-Notch signaling pathway were bidirectional. Together, hypoxia played an important role in TMJ-OA and accelerates angiogenesis of condylar cartilage through HIF-1-VEGF-Notch signaling pathway. HIF-1α and Notch might be novel therapeutic targets in TMJ-OA.

Efficacy of secondary closure technique after extraction of third molars: a meta-analysis.

The purpose of this study was to assess the influence of two suture methods on the postoperative complications of extraction of mandibular third molars (M3M). We searched the MEDLINE (PubMed), Cochrane Library, and Web of Science databases until 18 May 2018 for randomised controlled trials (RCT) that evaluated the influence of any suture techniques on postoperative complications after the removal of impacted M3M. Pain, facial swelling, and trismus were measured for both the early stage (2-3 days) and late stage (5-7 days) after extraction. We identified 655 records, of which five were assessed for eligibility. All trials included had a moderate risk of bias. The analysis showed that the patients whose wounds had been closed primarily had significantly more pain than those whose wounds were closed secondarily (a wedge of mucosa) during the early stage (standardised mean difference (SMD), -0.49; 95% CI -0.71 to -0.27; P<0.0001) and the late stage (SMD -0.36; 95% CI -0.54 to -0.19; P<0.0001) after the removal of impacted M3M. Patients whose wounds were closed secondarily had less swelling (mm) at the postoperative early stage (SMD -1.12; 95% CI -1.57 to -0.66; P<0.00001) and late stage (SMD -0.51; 95% CI -0.68 to -0.33; P<0.00001). There was more trismus in the primary closure group than in the secondary group during both stages. Our findings suggest that secondary closure causes less pain, facial swelling, and trismus in both early and late stages of surgical removal of impacted M3M, and therefore it improves the quality of life by reducing postoperative discomfort.