Stem Cells-Loaded 3D-Printed Scaffolds for the Reconstruction of Alveolar Cleft.

The advances in the field of tissue engineering and regenerative medicine have opened new vistas for the repair of alveolar clefts. However, the currently available biomaterials used for the repair of alveolar clefts have poor mechanical properties and biocompatibility, which hinders the treatment outcomes. Here, we aimed to develop 3D printed biomimetic scaffolds that fuses ß-tricalcium phosphate (ß-TCP) and bone marrow mesenchymal stem cells (BMSCs) for improving the repair of alveolar clefts. The methacrylate gelatin (GelMA) was mixed with ß-TCP for the preparation of GelMA/ß-TCP hybrid scaffolds via 3D printing platform and chemically cross-linking with UV light. The physicochemical properties of the hydrogel scaffolds were characterized. Moreover, the survival state, proliferation ability, morphological characteristics, and osteogenic induction of BMSCs were examined. The prepared hybrid scaffolds showed good biocompatibility and mechanical properties. BMSCs attached well to the scaffolds and proliferated, survived, differentiated, and stimulated osteogenesis for the reconstruction of alveolar clefts. We expect that use of the prepared hybrid hydrogel scaffold can improve the outcomes of alveolar cleft repair in clinic and expand the application of hybrid hydrogel in tissue engineering repair.

Blockade of Th17 response by IL-38 in primary Sjögren's syndrome.

BACKGROUND: T helper 17 (Th17) cell responses were involved in the pathophysiology of primary Sjögren's syndrome (pSS). IL-38 has been reported to inhibit the secretion of chemokines involved in Th17 pathway. This study aimed to explore the regulation of Th17 response by IL-38 in pSS. METHODS: Twenty-four pSS patients, 15 non-pSS control, and 13 health subjects were recruited. The expression of IL-38 and Th17 cytokines were detected and compared between pSS and controls. Human peripheral blood mononuclear cells (PBMCs) and minor salivary gland mononuclear cells (MSGMs) were purified and stimulated by IL-38. The differentiation and function of Th17 cells were evaluated by PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: The pSS patients presented with significantly lower expression of IL-38 and higher Th17 cytokines (IL-17 and IL-23) compared with both non-pSS and healthy controls. The IL-38 inhibited the differentiation and function of Th17 responses from PBMCs and MSGMs. The IL-38 treatment could inhibit the Th17 response in mice model. CONCLUSIONS: IL-38 inhibits T helper 17 type responses in pSS, suggesting that IL-38 may be used as potential treatment target in pSS.

[Effectiveness of Furlow palatoplasty in velopharyngeal insufficiency after cleft palate surgery].

OBJECTIVE: To explore the application value of Furlow palatoplasty in reconstruction of velopharyngeal insufficiency (VPI) after cleft palate surgery. METHODS: Between August 2015 and January 2017, 48 patients with VPI after cleft palate surgery were treated with Furlow palatoplasty. There were 29 males and 19 females, aged from 4 to 17 years (mean, 6.1 years). There were 16 cases of incomplete cleft palate and 32 cases of complete cleft palate; and 16 cases of soft cleft palate and 32 cases of soft and hard cleft palate. The interval between first cleft palate surgery and Furlow palatoplasty was 3 to 13 years (mean, 5.9 years). The patients were accompanied by significant open rhinolalia and nasal leakage. The degree of velopharyngeal closure assessed by electronic nasopharyngeal fiberoptic endoscopy was grade Ⅲ. The operation time and intraoperative blood loss were recorded. The total length of palate, the length of soft palate, the depth of pharyngeal cavity, and the width of pharynx and palate arch were measured before operation and at immediate after operation, and the change of the above indexes before and after operation was calculated. According to the results of clinical assessment, the patients were allocated into three groups: velopharyngeal competence (VPC) group, marginal velopharyngeal inadequacy (MVPI) group, and VPI group. The relationship between the soft palate and the posterior pharyngeal wall was evaluated by lateral cephalometric radiographs at 3 months after operation, and the patients were allocated into complete contact group, point contact group, and non-contact group. The velopharyngeal closure was evaluated by electronic nasopharyngeal fiberoptic endoscopy (grade Ⅰ, Ⅱ, Ⅲ). Spearman analysis was used to analyze the correlation between the changes of the total length of palate, the length of soft palate, the depth of pharyngeal cavity, and the width of pharynx and palate arch before and after operation. The contact degree of soft palate and posterior pharyngeal wall and the closure degree of pharynx and palate were grouped separately, and the above indexes were analyzed statistically. RESULTS: The operation time was 35-64 minutes (mean, 41 minutes); the intraoperative blood loss was 3-10 mL (mean, 6 mL). All patients were followed up 3 months. After 3 months of operation, the clinical evaluation results were 34 cases of VPC, 7 cases of MVPI, and 7 cases of VPI. Lateral cephalometric radiographs showed that 30 cases had complete contact with the posterior pharyngeal wall, 11 cases had point contact, and 7 cases had no contact. Electronic nasopharyngeal fiberoptic endoscopy showed that the pharyngeal closure function was improved to varying degrees, 29 cases of grade Ⅰ, 12 cases of grade Ⅱ, and 7 cases of grade Ⅲ. There were significant differences in the total length of palate, the length of soft palate, the depth of pharyngeal cavity, and the width of pharynx and palate arch between pre- and post-operation ( P<0.05). Spearman correlation analysis showed a correlation between the change in the total length of palate before and after operation and the change in the length of soft palate ( r=0.448, P=0.001). There were significant differences in the changes of total length of palate, the length soft palate, and the depth of pharyngeal cavity before and after operation between VPC, MVPI, and VPI groups ( P<0.05); and there was no significant difference in the change of the width of pharynx and palate arch before and after operation between groups ( P>0.05). There were significant differences in the changes of total length of palate and the length soft palate before and after operation between complete contact, point contact, and non-contact groups ( P<0.05); and there was no significant difference in the change of the depth of pharyngeal cavity and the width of pharynx and palate arch before and after operation between groups ( P>0.05). CONCLUSION: Furlow palatoplasty can restore the VPI after cleft palate surgery, which can effectively prolong the soft palate and reduce the depth of the pharynx. It can cover the physiological and anatomical morphology of velopharyngeal closure significantly and improve the velopharyngeal function.

Three-Dimensional Printing of Personalized Nasal Stents for Patients With Cleft Lip.

OBJECTIVE: This report describes the design and printing of personalized nasal stents for cleft lip using 3-dimensional (3D) technology. MATERIALS AND METHODS: We used silicone rubber to make the impressions, a 3D laser scanner to obtain 3D data, and Dental SG resin cartridges as printing material. We printed the personalized nasal stents using a photosensitive resin printer. RESULTS: We placed the stents in patients after cleft lip surgery. They enabled personalized adjustment and good anastomosis, with a low probability of slipping from the nasal cavity. CONCLUSION: With this technique, we can provide good nasal support for patients with cleft lip.

Association between BMP4 gene polymorphisms and cleft lip with or without cleft palate in a population from South China.

OBJECTIVE: Previous studies have suggested an association between several polymorphisms of the BMP4 gene and susceptibility to non-syndromic cleft lip with or without cleft palate (NSCL/P) in various populations. However, this association may vary according to ethnic group and the form of NSCL/P. This study analyzed the association between the BMP4 gene polymorphisms rs762642, rs17563, and rs10130587 with the risk of cleft lip only (CLO), cleft palate only (CPO), and cleft lip with palate (CLP) in a population from South China. METHODS: This case-control study included 165 patients with NSCL/P (53 patients with CPO, 52 with CLO, and 60 with CLP) and 52 healthy volunteers. Peripheral blood samples were collected from all subjects to genotype the rs762642, rs17563, and rs10130587 polymorphisms by direct sequencing. Genotype and allelic frequencies of these polymorphisms were compared between healthy volunteers and patients with various forms of NSCL/P. RESULTS: The genotype and allelic frequencies of rs762642 differed significantly between subgroups (CPO and CLP) and normal controls, whereas a significant difference was observed only in the CLO subgroup for the rs17563 polymorphism and in the CLO and CLP groups for the rs10130587 polymorphism. In addition, we identified a novel association of a BMP4 gene polymorphism, which was in linkage disequilibrium with the rs10130587 polymorphism, with CLO and CLP. CONCLUSION: The BMP4 gene polymorphisms rs762642, rs17563, and rs10130587 exhibit different associations with different forms of NSCL/P, suggesting that different forms of NSCL/P may have different etiologies.

The Effect of Mandibular Distraction Osteogenesis on Weight Velocity in Infants With Severe Pierre Robin Syndrome.

Mandibular distraction osteogenesis (MDO) effectively improves airway obstruction in Pierre Robin syndrome (PRS) patients. However, whether or not early MDO is beneficial to the development of children is still controversial. To observe the influence of PRS patient age at the time of MDO on their development, the authors retrospectively analyzed preoperative and postoperative body weight in 41 children with PRS who underwent MDO treatment from 2014 to 2016. The body weight of the infants at the time of birth, first visit, MDO surgery, distractor removal, and palatoplasty surgery was recorded. The body weight percentile significantly fell from 34.4 ±â€Š5.8 at birth to 13.1 ±â€Š3.6 at the time of MDO (P < 0.001), and increased to 28.3 ±â€Š5.3 at distractor removal (P < 0.05) following MDO, finally reaching 42.4 ±â€Š6.5 at palatoplasty surgery (P < 0.001). The infants who accepted MDO treatment at <1 month of age maintained a significantly higher body weight percentile than those who accepted MDO surgery at 1 to 3 months or 4 to 7 months of age, at the time of both MDO and palatoplasty surgeries (P < 0.05). After the MDO procedure, the body weight percentiles of the PRS infants with a cleft palate were comparable to those without a cleft palate at the time of palatoplasty surgery. The body weight percentile quickly climbed to 74.0 ±â€Š35.2 at the time of distractor removal, from 46.7 ±â€Š18.2 at the time of MDO. In conclusion, early MDO was beneficial in severe cases of PRS for patients to recover body weight and to allow for earlier palatoplasty surgery.

Knockdown of Cdc6 inhibits proliferation of tongue squamous cell carcinoma Tca8113 cells.

The present study aimed at evaluating the effects of Cdc6 downregulation on the proliferation of Tca8113 cells. Two lentiviral vectors (KD1 and KD2) expression cdc6 siRNA were constructed and then infected into Tca8113 cells. Real-time PCR and Western blot analysis were performed to detect the mRNA and protein expression of Cdc6. MTT assays were employed to delineate the growth curves, and flow cytometry was performed to assess cell-cycle progression and apoptosis in Tca8113 cells. Following infection with the lentiviral vectors, real-time PCR and Western blot analysis revealed that Cdc6 expression was markedly suppressed in Tca8113 cells. When compared with the negative control group, the mRNA expression of Cdc6 was reduced by 50% and 65% and the protein expression by 65.87% and 79.38% in cells harboring KD1 or KD2, respectively. Cell growth was slowed, and the growth inhibition rate was 25.84% and 30.34% in Tca8113 cells following infection with KD1 or KD2, respectively. In addition, cell-cycle progression was altered. In KD- infected Tca8113 cells, the proportion of cells in the S phase was markedly reduced, but the proportion in the G1 phase was significantly increased; this was accompanied by an increase in cell apoptosis. Downregulation of Cdc6 effectively inhibited the proliferation of Tca8113 cells.

Expression characteristics of astrocyte elevated gene-1 (AEG-1) in tongue carcinoma and its correlation with poor prognosis.

Astrocyte elevated gene-1 (AEG-1) expression is increased in diverse human cancers and plays a vital role in tumorigenesis and progression. The aim of this study was to investigate the clinicopathologic features and prognostic significance of AEG-1 in squamous cell carcinoma of the tongue (TSCC). Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in paraffin-embedded tissues from 93 patients with TSCC. Real-time PCR and western blot analyses were employed to examine AEG-1 expression in 4 pairs of primary TSCC and adjacent non-cancerous tissues from the same patient. Immunohistochemical results revealed that the positive rate for AEG-1 in TSCC tissues (48.39%, 45/93) was higher than that in the normal tongue tissues (10.00%, 3/30) (P < 0.001). These results were further confirmed between TSCC tissues and matched adjacent non-cancerous tissues by Western blot and RT-PCR. Simultaneously, AEG-1 protein level was positively correlated with differentiation degree (P < 0.001), clinical stage (P < 0.001), T classification (P = 0.007) and N classification (P = 0.012). Furthermore, patients with higher AEG-1 expression had shorter overall survival time. Multivariate analysis (Cox regression) also suggested that AEG-1 expression was an independent prognostic indicator for TSCC (P = 0.043). Our results indicate that AEG-1 expression is closely associated with carcinogenesis and progression of TSCC, and may represent a novel and valuable predictor for prognostic evaluation of TSCC patients.

Pulmonary metastases from an Ameloblastoma: case report and review of the literature.

Ameloblastomas have a high recurrence rate, and because of their biological tendency towards local invasion are considered borderline tumours. Despite this, reports of metastasis of these tumours are rare. This report presents a patient with mandibular ameloblastoma that recurred 29 years after surgery and metastasized to both lungs. Because of the large range of the area of metastasis, complete surgical resection of the tumours was impossible. After confirming the diagnosis by biopsy of the pulmonary lesions the pulmonary metastases were not treated actively. Observation over 4 years showed no obvious change in the lung metastasis. Recent cases are summarized and analyzed in this paper, with respect to its occurrence, pathological types, methods of treatment and other related aspects.