Morphological Changes of the Temporomandibular Joint and Masseter Muscle After Mandibular Angle Osteotomy.

Mandibular angle osteotomy with outer cortex grinding is an effective cosmetic procedure for correcting square faces. However, morphological changes in the mandible may also cause temporomandibular joint (TMJ) disorders. This retrospective study aimed to investigate the morphological stabilization of the TMJ and changes in masseter muscle thickness after mandibular angle osteotomy to evaluate the safety of the procedure. Data from patients who underwent mandibular angle osteotomy with outer cortex grinding between January 2016 and January 2019 were retrospectively reviewed. Preoperative and long-term follow-up (~1 y) computed tomography data were collected from these patients, and morphological changes in the TMJ and masseter muscle were analyzed. The results from the computed tomography data showed that the condylar length and condylar height were significantly reduced 1 year after the operation (P < 0.05). In addition, the morphology of the TMJ was stable, and the distance between the mandibular condyle and the glenoid fossa did not change significantly. No significant difference was observed in masseter muscle thickness before and after the operation. After mandibular angle osteotomy with outer cortex grinding, the length and height of the mandibular condyle were functionally restored without any disorders of the TMJ. Moreover, the masseter muscle exhibited stable function. In conclusion, the procedure is safe for occlusal function and suitable for popularization.

Prediction of the Postoperative Bone Regeneration Rate After Mandibular Reduction: From the Perspective of Preoperative Inflammatory and Immune Status.

BACKGROUND: Following mandibular reduction, bone regeneration in the angle region is a problem that can affect facial aesthetics and lead to revision surgery. The bone regeneration rate (BRR) varies between individuals and is difficult to predict. However, studies focusing on preoperative patient-related factors are lacking. As bone regeneration is closely related to the inflammatory and immune status of the organism, according to in vitro and in vivo evidence, preoperative inflammatory indicators were included in this study as potential predictors. METHODS: Demographic and preoperative laboratory data were included as independent variables. The BRR calculated from computed tomography data was included as the dependent variable. Univariate analysis and multiple linear regression analysis were used to determine the key factors influencing the BRR. The ROC curves were used to analyse the corresponding predictive efficacy. RESULTS: 23 patients (46 mandibular angles) fulfilled the inclusion criteria. The mean bilateral BRR was 23.82 ± 9.90%. Preoperative monocyte count (M) was an independent positive factor for BRR, and age was a negative factor. Only M had a good predictive ability, and its optimal cut-off point to distinguish patients with BRR greater than 30% was 0.305 × 109/L. Other parameters were not significantly correlated with BRR. CONCLUSIONS: Patient age and preoperative M may influence BRR, with M having a positive effect and age having a negative effect. According to the preoperative blood routine tests that are readily available, using the diagnostic threshold (M [Formula: see text] 0.305 × 109/L) derived from this study, surgeons can better predict BRR and identify patients whose BRR is greater than the mean level. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Epicanthoplasty With Rotated-advanced-back Cut Flap.

BACKGROUND: Epicanthoplasty is one of the most popular cosmetic surgeries in Asia. The aim of this study was to present a rotated, advanced, back cut flap (R-A-B flap) that leads to correct the congenital epicanthus effectively with satisfactory results. METHODS: From January of 2017 to December of 2018, we performed the modified cut back flap epicanthoplasty to correct epicanthus. The esthetic results were evaluated with patients' feedback: perfect, good, dissatisfied, or failed. RESULTS: A total of 118 patients were involved. Postoperative evaluation using a grading scale indicated "perfect" results for 86 patients (73%) and "good" results for 32 patients (27%). No patients rated the results as "dissatisfied" or "failed." There were no significant postoperative complications. CONCLUSION: The R-A-B flap for epicanthoplasty is a reliable and simple method, resulting in good cosmetic outcome with minimal scar formation.

Relationship Between Masticatory Muscle Size and Bone Regeneration After Mandibular Angle Osteotomy.

ABSTRACT: Mandibular angle osteotomy with outer cortex grinding has become the preferred cosmetic procedure for correcting square faces. After surgery, bone hyperplasia at the mandibular angle affects the operation result. This study evaluated the effect of the masticatory muscles on bone repair. From January 2016 to January 2019, patients who underwent mandibular angle osteotomy with outer cortex grinding were retrospectively reviewed. Computed tomography data of these patients were collected, and the bone volume of the mandibular angle changes and its correlation with masticatory muscle morphology were analyzed. Computed tomography data measurement results showed that a large amount of bone in the mandibular angle area was removed by the operation; however, the long-term follow-up results showed that there was bone hyperplasia in the mandibular angle areas. Compared with the immediate postoperative bone volume, the difference was statistically significant (P < 0.01). The thickness and cross-sectional area of the masseter muscle were significantly related to bone regeneration (P < 0.01). This study suggests that mandibular angle osteotomy with outer cortex grinding could ablate the symptoms of a prominent mandibular angle; however, muscle-related bone hyperplasia in the mandibular angle area after surgery was a non-negligible event, which may significantly compromise surgical outcomes.

Craniofacial and Upper Airway Development in Patients With Treacher Collins Syndrome.

ABSTRACT: This study evaluated age-associated morphology changes in the cranial base, facial development, and upper airway of patients with Treacher Collins syndrome (TCS). A total of 33 preoperative computed tomographic images (TCS, n = 14; control, n = 19) were included in the study and divided into three age-related subgroups (2-6 years, 7-18 years, and older than 18 years). Linear, angular cephalometric measurements and upper airway volumes were collected. All measurements were analyzed using ProPlan CMF software (version 3.0; Materialize, Leuven, Belgium). The association between aging and upper airway morphology was analyzed. Compared to control subjects, TCS patients had a smaller cranial base, maxilla, and nose; they also had reduced upper airway volume compared to control subjects. The observed differences were most significant in patients between the ages of 7 and 18 years. This study used computed tomography-based three-dimensional analyses to provide a detailed description of age-related changes that occur in craniofacial measurements and upper airway volumes in children, adolescents, and young adult patients with TCS in China. These data can be used to evaluate individual patients with TCS and to select treatment to improve the growth of the craniofacial region.

Downregulation of lncRNA DANCR promotes osteogenic differentiation of periodontal ligament stem cells.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been widely known to have an appreciable effect in physiology and pathology. In tooth regeneration, periodontal ligament stem cells (PDLSCs) are regarded as a key effector, whereas, how lncRNA acts in the osteogenic differentiation of PDLSCs have not been completely understood. This study aims to find out the relationship between lncRNA DANCR and the proliferation and osteogenic differentiation of PDLSCs. METHODS: Microarray was used to observe the different expression of lncRNAs in differentiated and undifferentiated PDLSCs. And then osteogenic-related lncRNA, DANCR was screened out. Its effects on proliferation and osteogenic differentiation was explored by constructing an overexpression and inhibition model. qRT-PCR was used to detect the mRNA expression of osteogenesis related genes. MTT assay was performed to assess the effects of DANCR on cell growth curve. To quantify the effects of DANCR on osteogenic differentiation of PDLSCs, ALP staining and alizarin red was performed in basic culture medium and osteogenic medium. Data were statistically processed. RESULTS: Compared with the undifferentiated PDLSCs, the alizarin red staining level was higher in differentiated PDLSCs. And the expressions of osteogenic differentiation marker genes Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and bone morphogenetic protein (BMP-2) were significantly increased in the differentiated PDLSCs. Furthermore, we noticed that comparing with control groups, the expression of lncRNA DANCR decreases markedly in osteogenically induced PDLSCs. DANCR promoted proliferation of PDLSCs, as evidenced by cell viability. Further investigation has proven that the downregulation of DANCR shows in the calcium sediment forming, alkaline phosphatase (ALP) activation and some osteogenic-related gene markers' upregulation including Runx2, OCN and BMP-2, which finally results in the osteogenic differentiation of PDLSCs following the transfection and induction. Conversely, DANCR upregulation was shown to repress the osteogenic differentiation potential of PDLSCs. CONCLUSIONS: The osteogenic differentiation of PDLSCs has proven to related to the down regulation of lncRNA DANCR. And this paper throws light on the effects of DANCR in the process of PDLSCs' osteogenic differentiation.

Application of the Bracing System in Reduction Malarplasty in Asian Population.

BACKGROUND: In the East, a broad and prominent malar is considered to express an aggressive and unpleasing impression; therefore, patients seek to improve their appearance through malar reduction. Although most of the techniques have been greatly improved, still there are some pitfalls in the form of cheek sagging or bone nonunion. In this study, we performed a reduction malarplasty using a firm bracing system to minimize major postoperative complications. METHOD: This was a retrospective study evaluating the results of a total of 157 patients (139 women and 18 men) who underwent reduction malarplasty using a bracing system via intraoral and periauricular. The age of the patients ranged from 17 to 44 with a mean age of 25.3 years. The mean follow-up period was 9.4 months. All patients underwent routine physical and laboratory examinations. Facial photographs in the frontal, oblique, and submentovertical views were taken. Patients with severe facial asymmetry and facial deformities were excluded from the study. Preoperative states and patients' desires were considered. In some patients, combined malarplasty with mandibular angle reduction or genioplasty was performed. RESULTS: A total of 157 patients who underwent this modified reduction malarplasty between January 2015 and January 2019 were retrospectively reviewed. Decent postoperative facial stability and satisfactory aesthetic results were realized among all patients. Major complications such as severe asymmetry or bone nonunion were not observed in our patients. CONCLUSION: Based on a thorough anatomic understanding of zygoma and masseter action, we modified previous L-shaped reduction malarplasty through constructing a firm bracing system on the malar complex. Satisfactory surgical outcomes were obtained. Our method is an ideal surgical method to effectively reduce the height and width of the zygomatic arch and prevent complications such as bone nonunion and cheek drooping. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Icariin Reduces Cartilage Degeneration in a Mouse Model of Osteoarthritis and is Associated with the Changes in Expression of Indian Hedgehog and Parathyroid Hormone-Related Protein.

BACKGROUND The aim of this study was to determine the role of icariin, a Chinese traditional herbal medicine extracted from Epimedium, in osteoarthritis (OA), using the murine anterior cruciate ligament transection (ACLT)-induced model of OA and micromass culture of murine chondrocytes. MATERIAL AND METHODS Twenty-four three-month-old C57/6J mice were randomly divided into three groups: the sham group (no surgery and joint injection with normal saline) (N=8); the ACLT + ICA group (ACLT surgery and icariin treatment) (N=8); and the ACLT group (ACLT surgery and joint injection with normal saline) (N=8). At 12 weeks after ACLT surgery, murine articular cartilage was harvested from all mice for histological evaluation of any differences in cartilage degeneration. In vitro micromass culture of mouse chondrocytes was used to study the effects of icariin on chondrocyte differentiation and growth from the three mouse groups. RESULTS Icariin treatment (mice in the ACLT + ICA group) significantly reduced degeneration of cartilage in OA with increased cartilage thickness, associated with increased expression of collagen type II alpha 1 (COL2A1), decreased chondrocyte hypertrophy, and decreased expression of collagen type X (ColX) and matrix metalloproteinase 13 (MMP13). In vitro, icariin promoted chondrocyte differentiation by upregulating the expression of agrrecan, Sox9 and parathyroid hormone-related protein (PHrP) and down-regulation of Indian hedgehog (Ihh) and genes regulated by Ihh. CONCLUSIONS In a mouse model of OA icariin treatment reduced destruction of cartilage, promoted chondrocyte differentiation, upregulated expression of PHrP and down-regulated the expression of Ihh.

Biological Effects of Orthodontic Tooth Movement Into the Grafted Alveolar Cleft.

PURPOSE: Functional stimulus during orthodontic tooth movement into the grafted bone can lead to better alveolar bone grafting outcomes. The aim of this study was to analyze the biological effects of orthodontic tooth movement into the grafted alveolar cleft area with histologic staining, fluorescence staining, and real-time polymerase chain reaction (PCR). MATERIALS AND METHODS: An animal model of orthodontic tooth movement into the grafted alveolar cleft area was established in 8-week-old Sprague-Dawley rats. The animals were divided into the experimental group and the control group. Four checkpoints were observed: before orthodontic stimuli, day 1 after orthodontic stimuli, day 3 after orthodontic stimuli, and day 5 after orthodontic stimuli. The cleft bone formation conditions, including the collagen fibers and the activities of the osteoclasts and osteoblasts, were evaluated by histologic staining. The expression of tartrate-resistant acid phosphatase (TRAP), receptor activator nuclear factor κB ligand, and Runt-related transcription factor 2 was detected by real-time PCR in both groups. RESULTS: Hematoxylin-eosin staining showed that the remodeling process of iliac autografts was completed when the orthodontic stress was applied, whereas the bone tissues first showed osteoclastogenesis and then osteogenesis. On the basis of TRAP staining, the osteoclasts increased to the maximal amount on day 3 and decreased thereafter. Evidence from tetracycline fluorescence staining indicated that no obvious changes in osteoblast activity were detected at the early stage; however, it gradually increased, especially in the region close to the root surface. According to real-time PCR, the expression of TRAP increased in both the early and middle stages, that of receptor activator nuclear factor κB ligand increased in the early stage, and that of Runt-related transcription factor 2 increased in the late stage. Moreover, the results showed significant differences between the experimental and control groups. CONCLUSIONS: Orthodontic tooth movement into the alveolar cleft bone graft area promoted bone remodeling of embedded bone, thus inducing bone resorption and subsequent deposition.

Icariin: does it have an osteoinductive potential for bone tissue engineering?

Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi-component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Most interestingly, it has been reported that icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. This review focuses on the performance of icariin in bone tissue engineering and on blending the information from icariin with the current knowledge relevant to molecular mechanisms and signal pathways. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti-osteoporosis, osteogenesis, anti-osteoclastogenesis, chondrogenesis, angiogenesis, and anti-inflammation. The osteoinductive potential and the low price of icariin make it a very attractive candidate as a substitute of osteoinductive protein-bone morphogenetic proteins (BMPs), or as a promoter for enhancing the therapeutic effects of BMPs. However, the effectiveness of the local delivery of icariin needs to be investigated further.

Repair of critical-sized rat calvarial defects using genetically engineered bone marrow-derived mesenchymal stem cells overexpressing hypoxia-inducible factor-1α.

The processes of angiogenesis and bone formation are coupled both temporally and spatially during bone repair. Bone marrow-derived mesenchymal stem cells (BMSCs) have been effectively used to heal critical-size bone defects. Enhancing their ability to undergo angiogenic and osteogenic differentiation will enhance their potential use in bone regeneration. Hypoxia-inducible factor-1α (HIF-1α) has recently been identified as a major regulator of angiogenic-osteogenic coupling. In this study, we tested the hypothesis that HIF-1α gene therapy could be used to promote the repair of critical-sized bone defects. Using lentivirus-mediated delivery of wild-type (HIF) or constitutively active HIF-1α (cHIF), we found that in cultured BMSCs in vitro, HIF and cHIF significantly enhanced osteogenic and angiogenic mRNA and protein expression when compared with the LacZ group. We found that HIF-1α-overexpressing BMSCs dramatically improved the repair of critical-sized calvarial defects, including increased bone volume, bone mineral density, blood vessel number, and blood vessel area in vivo. These data confirm the essential role of HIF-1α modified BMSCs in angiogenesis and osteogenesis in vitro and in vivo.

The osteogenesis effect of rhBMP2-loaded calcium phosphate cements in repairing dental extraction sockets.

PURPOSE: After extracting impacted mandibular third molars (IMM3), the resulting bone loss at the distal surface of the distal root of mandibular second molars (MM2) is responsible for the poor stability of MM2. This study aimed to identify the clinical osteogenesis effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate cements (CPCs) and rhBMP-2 delivery systems (rhBMP-2/CPCs, named CPCII) on bone loss repair at the distal surface of the MM2 distal root after IMM3 extraction. METHODS: Written informed consent was obtained from every participant whose IMM3 needed extraction. The impact of IMM3 on both sides was basically identical. From April 2014 to March 2016, extraction of IMM3 was performed in 9 patients (5 males/4 females, 26-42 years old). One side was randomly selected as the experimental group, and CPCII systems were implanted into the distal surface of the distal root in dental extraction sockets. The wounds on the other side were sutured and allowed to heal naturally (be treated as the control group). New bone formation in the alveolar fossa was detected 3 and 12 months after the operation by cone-beam computed tomography (CBCT) to measure the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CAR). RESULTS: The CAR-CEJ distance on the test side was less than that on the control side (P<0.5). CONCLUSION: The quantity of new bone formation in the experimental group was greater than that in the control group. CPCII systems have osteogenic potential in the healing process of tooth extraction sockets.

Repair of bone defects around dental implants with bone morphogenetic protein/fibroblast growth factor-loaded porous calcium phosphate cement: a pilot study in a canine model.

OBJECTIVES: To study the effects of the bone morphogenetic protein-2 (BMP-2)/fibroblast growth factor (bFGF)-loaded porous calcium phosphate cement (CPC) on the repair of bone defects around dental implants. MATERIAL AND METHODS: Thirty critical-sized bone defects in beagle dogs were repaired with engineered bone composed of autologous bone-marrow-derived mesenchymal stem cells (BMSCs), BMP-2, bFGF and CPC. Repairs were divided into six groups: BMSC/BMP-2/bFGF/CPC, BMSC/BMP-2/CPC, BMSC/bFGF/CPC, BMSC/CPC, CPC and no treatment. Polychrome sequential fluorescent labels were also performed post-operatively. Fluorescence histological examinations of undecalcified sections at post-operative week 12 were performed to clarify changes in the new bone around the dental implants. RESULTS: The animals exhibited a perfect post-operative course, with none experiencing any infection. Undecalcified sections showed that new bone was actively formed in the BMP-2/bFGF group after 12 weeks. The bone mineralization apposition rate was better in the BMP-2/bFGF group than in the other groups (P<0.05). CONCLUSION: BMP-2 and bFGF together are more effective than either one alone in promoting the formation of new bone and may exert a synergistic activity at bone defects around dental implants.

Heterotrophic ossification on a skin graft in a postburn scar of the chin.

Some patients who have heterotrophic ossification (HO) in a postburn scar are occasionally seen in the clinic. The occurrence of HO following hip and abdominal surgery is common in males, whereas females are frequently affected following burns. The HO of skin grafts in burn scars of the superior body parts is uncommon, especially on the face. We report a recent case of a male patient in whom HO arose on skin grafts on his chin. The patient presented with a history of a painless chin mass for 48 years. Computed tomography scan suggested that the mass was located within subcutaneous tissue away from the lower jaw. The density of the mass was almost the same as the cortical bone of the lower jaw. The mass was completely resected under general anesthesia. It was a rectangular mass of 3× 0.5× 0.3 cm. Histological examination gave the diagnosis of HO, which was also confirmed by immunohistochemical stainings for vimentin. Recurrence was not found in this case by clinical and radiologic follow-up at 1 year after surgery.

[A method for generating dental panoramic radiographs from 3D CT sectional data].

In this paper, a new method was presented which can generate dental panoramic radiographs from the 3D CT sectional data. The dental panoramic radiograph was generated by casting ray into the 3D sectional data from a curved surface close to the dental arch. With this method, the relationship between the 3D CT sectional data and the dental panoramic radiographs was built, which helped to overcome the defects in the real X-ray panoramic radiographs, such as structure overlap and unselectable content for displaying. The technology is of certain significance in computer aided technique and surgical planning related to dentistry.

[Experimental study on adipose-derived stem cells amplified by silk fibroin/poly- L-lactic acid microcarriers in vitro].

OBJECTIVE: To investigate the effect of silk fibroin-poly- L-lactic acid (SF-PLLA) microcarriers on the expansion and differentiation of adipose-derived stem cells (ADSCs). METHODS: ADSCs were extracted from adipose tissue donated voluntarily by patients undergoing liposuction by enzymatic digestion. The 3rd generation ADSCs were inoculated on CultiSpher G and SF-PLLA microcarriers (set up as groups A and B, respectively), and cultured in the rotary cell culture system. ADSCs cultured in normal two-dimensional plane were used as the control group (group C). Scanning electron microscope was used to observe the microcarriers structure and cell growth. Live/Dead staining and confocal fluorescence microscope was used to observe the distribution and survival condition of cells on two microcarriers. DNA quantification was used to assess cell proliferation on two microcarriers. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect chondrogenesis, osteogenesis, and adipogenesis related gene expression of ADSCs in 3 groups cultured for 18 days. Flow cytometry was used to identify the MSCs surface markers of ADSCs in 3 groups cultured for 18 days, and differential experiments were made to identify differentiation ability of the harvested cells. RESULTS: ADSCs could be adhered to and efficiently amplified on the two microcarriers. After 18 days of cultivation, the total increment of ADSCs of the two microcarriers were similar ( P>0.05). qRT-PCR results showed that chondrogenesis related genes (aggrecan, cartilage oligomeric matrix protein, SOX9) were significantly up-regulated for ADSCs on SF-PLLA microcarriers and adipogenesis related genes (peroxisome proliferator-activated receptor γ, lipoprotein lipase, ADIPOQ) were significantly up-regulated for ADSCs on CultiSpher G microcarriers, all showing significant differences ( P<0.05). Flow cytometry and differentiation identification proved that the harvested cells of the two groups were still ADSCs. CONCLUSION: The ADSCs can be amplified by SF-PLLA microcarriers, and the chondrogenic differential ability of harvested cells was up-regulated while the adipogenic differential was down-regulated.

[Experimental study on tissue engineered cartilage constructed by three-dimensional bioprinted human adipose-derived stem cells combined with gelatin methacryloyl].

OBJECTIVE: To explore the feasibility of three-dimensional (3D) bioprinted adipose-derived stem cells (ADSCs) combined with gelatin methacryloyl (GelMA) to construct tissue engineered cartilage. METHODS: Adipose tissue voluntarily donated by liposuction patients was collected to isolate and culture human ADSCs (hADSCs). The third generation cells were mixed with GelMA hydrogel and photoinitiator to make biological ink. The hADSCs-GelMA composite scaffold was prepared by 3D bioprinting technology, and it was observed in general, and observed by scanning electron microscope after cultured for 1 day and chondrogenic induction culture for 14 days. After cultured for 1, 4, and 7 days, the composite scaffolds were taken for live/dead cell staining to observe cell survival rate; and cell counting kit 8 (CCK-8) method was used to detect cell proliferation. The composite scaffold samples cultured in cartilage induction for 14 days were taken as the experimental group, and the composite scaffolds cultured in complete medium for 14 days were used as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was performed to detect cartilage formation. The relative expression levels of the mRNA of cartilage matrix gene [(aggrecan, ACAN)], chondrogenic regulatory factor (SOX9), cartilage-specific gene [collagen type Ⅱ A1 (COLⅡA1)], and cartilage hypertrophy marker gene [collagen type ⅩA1 (COLⅩA1)] were detected. The 3D bioprinted hADSCs-GelMA composite scaffold (experimental group) and the blank GelMA hydrogel scaffold without cells (control group) cultured for 14 days of chondrogenesis were implanted into the subcutaneous pockets of the back of nude mice respectively, and the materials were taken after 4 weeks, and gross observation, Safranin O staining, Alcian blue staining, and collagen type Ⅱ immunohistochemical staining were performed to observe the cartilage formation in the composite scaffold. RESULTS: Macroscope and scanning electron microscope observations showed that the hADSCs-GelMA composite scaffolds had a stable and regular structure. The cell viability could be maintained at 80%-90% at 1, 4, and 7 days after printing, and the differences between different time points were significant ( P<0.05). The results of CCK-8 experiment showed that the cells in the scaffold showed continuous proliferation after printing. After 14 days of chondrogenic induction and culture on the composite scaffold, the expressions of ACAN, SOX9, and COLⅡA1 were significantly up-regulated ( P<0.05), the expression of COLⅩA1 was significantly down-regulated ( P<0.05). The scaffold was taken out at 4 weeks after implantation. The structure of the scaffold was complete and clear. Histological and immunohistochemical results showed that cartilage matrix and collagen type Ⅱ were deposited, and there was cartilage lacuna formation, which confirmed the formation of cartilage tissue. CONCLUSION: The 3D bioprinted hADSCs-GelMA composite scaffold has a stable 3D structure and high cell viability, and can be induced differentiation into cartilage tissue, which can be used to construct tissue engineered cartilage in vivo and in vitro.

[Three-dimensional measurement analysis of midface morphology in Treacher Collins syndromes].

OBJECTIVE: To three-dimensionally calculate the craniofacial parameters of midface of patients with Treacher Collins syndrome (TCS) in China, in order to understand the changes in the spatial position relationship between the various anatomical structures of the midface. METHODS: CT imaging data of TCS patients and age- and gender-matched normal populations between January 2013 and July 2020 was retrospectively analyzed. A total of 33 cases met the selection criteria for inclusion in the study, including 14 cases in the TCS group and 19 cases in the control group. ProPlan CMF 3.0 software was used to perform three-dimensional digital reconstruction of the craniofacial bone, measure the anatomical parameters of the midface, and analyze its morphological structure; at the same time perform three-dimensional digital reconstruction of the upper airway for morphological analysis (measure upper airway volume). RESULTS: CT images analysis revealed that all 14 patients with TCS presented the typical features with downward slanting of the palpebral fissures and different degrees of zygomatico-orbital complex dysplasia. Cephalometric and morphological analysis of the midface revealed that, multiple transverse diameters of the midface of TCS patients were significantly decreased when compared with the control group ( P<0.05), such as the width of the maxillary base, the length of the maxillary complex, and some distances related to the nasal morphology; but the distance between bilateral orbitales increased in TCS group ( P<0.05). Several anteroposterior distances in TCS group were decreased significantly when compared to control group and the distance between the skull base point and the posterior nasal spine was the most shortened ( P<0.05). But there was no significant difference of the distance between nasion and anterior nasal spine, which represented anterior midface height, between groups ( P>0.05). The skull base angle and SNB angle (the angle between the sella point-nose root point-inferior alveolar seat point) of the TCS group both decreased when compared with the control group ( P<0.05), but there was no significant difference in SNA angle (the angle between the sella point-nose root point-upper alveolar seat point) between the two groups ( P>0.05). The total volume of the upper airway was (24 621.07±8 476.63) mm 3 in the TCS group, which was significantly lower than that of the control group [(32 864.21±13 148.74) mm 3] ( t=2.185, P=0.037). CONCLUSION: The transverse distances, anteroposterior distances, and multiple craniofacial angles measurement of TCS patients were significantly decreased when compared to the control group, presented with different degrees of zygomatico-orbital complex dysplasia, nasal and maxillary dysplasia, but there was no obvious restriction in face height development. Reduced internal diameters of the upper airway maybe responsible for the decreased upper airway volume of patients with TCS.

Cordycepin suppresses the migration and invasion of human liver cancer cells by downregulating the expression of CXCR4.

Liver cancer is a worldwide threat to human health. High expression levels of C­X­C chemokine receptor type 4 (CXCR4) have been reported to promote the migration and invasion capacities of liver cancer cells. Cordycepin, extracted from Cordyceps militaris, has anti­inflammatory, antioxidant and anticancerous properties. Therefore, in the present study, migration assays, western blotting, reverse transcription­quantitative PCR and immunofluorescence analyses were conducted to determine whether cordycepin was able to suppress the migration and invasion abilities of liver cancer cells by inhibiting CXCR4 expression. The results suggested that cordycepin notably inhibited migration and invasion, and decreased the expression of CXCR4 in a dose­dependent manner. Activation of phosphorylated (p­) NF­κB inhibitor α (IκBα) and p­P65, the principal components of the NF­κB signaling pathway, was also downregulated. In addition, cordycepin markedly suppressed the nuclear translocation of P65, but had no effect on the expression of total IκBα (t­IκBα) and total P65 (t­P65). JSH­23, an inhibitor of the NF­κB pathway, impaired the migration of liver cancer cells, and was found to act synergistically with cordycepin. Furthermore, cordycepin treatment reduced the chemotactic migration ability of liver cancer cells to stromal cell­derived factor 1 (SDF1), which was significantly enhanced following treatment with JSH­23. Collectively, the present results indicated that cordycepin inhibited the nuclear translocation of P65 by preventing p­IκBα activation; this resulted in the downregulation of CXCR4 expression, and subsequently, in the impaired migration and invasion abilities of liver cancer cells and attenuated reactivity to SDF1. The current study revealed a novel mechanism for the antimetastatic activity of cordycepin and its potential to exert positive synergistic effects with other compounds for the treatment of liver cancer.

Can baseline magnetic resonance angiography (MRA) status become a foremost factor in selecting optimal acute stroke patients for recombinant tissue plasminogen activator (rt-PA) thrombolysis beyond 3 hours?

OBJECTIVE: We investigated whether baseline vessel status evaluated by magnetic resonance angiography (MRA) can be the foremost factor to classify acute ischemic stroke patients into subgroups for thrombolytic therapy within 3-6 hours of symptom onset. METHODS: Acute ischemic stroke patients beyond 3 hours after symptom onset were examined by stroke magnetic resonance imaging (MRI) (diffusion- and perfusion-weighted imaging, and MRA) before and after thrombolysis treatment within 24-48 hours. Stroke MRI was used to classify acute ischemic stroke patients into subgroups and select optimal patients for thrombolytic treatment. Clinical scores were compared to determine whether there were significant differences among subgroups. RESULTS: The difference in day 90 modified Rankin scale (mRS) between treated salvageable and untreated salvageable patients with recombinant tissue plasminogen activator (rt-PA) was remarkably statistically significant (p=0.02). Treated salvageable patients had more favorable clinical outcomes as compared with the untreated salvageable patients. Patients who did not have baseline artery occlusion were associated with more favorable clinical outcomes than untreated salvageable patients (p<0.001). The difference between treated salvageable and patients without artery occlusion in 90 day mRS score was not statistically significant (p=0.058). CONCLUSION: Baseline vessel status evaluated by MRA may be used as the first factor ahead of mismatch to categorize acute ischemic stroke patients into subgroups. Patients who do not have initial vessel occlusion may not need thrombolytic therapy.