Bioinformatics Analysis of Hub Genes in Craniofacial Microsomia Combined With Congenital Heart Disease.

OBJECTIVE: The primary objective of this study was to investigate potential mechanisms and explore hub genes of craniofacial microsomia (CFM) patients associated with congenital heart defects (CHD). METHODS: Initially, the authors acquired target gene data related to CFM and congenital cardiac anomalies. Subsequently, the authors established a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were conducted using Metascape. Finally, the authors hub genes were screened by the cytoHubba plugin. RESULTS: A total of 43 CFM genes and 120 optimal CHD candidate genes were selected. The PPI networks for pathogenic genes contained 163 nodes and 1179 edges. Functional enrichment analysis largely focused on tissue formation and development. Five modules were identified from the PPI network, and 7 hub genes were screened out. The genes most relevant to CFM associated with congenital cardiac anomalies pathogenesis included fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of CFM associated with CHD by bioinformatics analyses. Our findings indicate that gene subfamilies fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein may have had significant involvement in both CFM and CHD.

Combined Genioplasty and External Oblique Line Grafting: An Innovative Method to Improve Lower Facial Contour.

BACKGROUND: Microgenia and the accompanying plump cheeks or hamster-like facial contour are all unattractive appearances among the Asian. Genioplasty with autogenous bone grafting is one of the effective ways to improve microgenia, in which a suitable donor area with less additional damage, lower infection rate, and more excellent effect is crucial. METHODS: Patients who had undergone genioplasty and autogenous external oblique line grafting (G-EOL) were followed up. The operation-related complications, preoperative, and long-term follow-up 3-dimensional spiral computed tomography (3D-CT) were collected and analyzed. RESULTS: Eight female patients who had received G-EOL and received 1 to 3 years of follow-up were included in this study. There were no short-term or long-term complications. CT data of bone of 8 patients and CT data of soft tissue of 6 patients at the preoperative and long term were compared. Through comparing CT data, the width at the level of the intersection of EOL and mandibular body, and the protrusion of the bony chin had improved significantly; the P values were all <0.001. Through measuring the soft tissue and analyzing the data, the ratio of lower and middle facial width, and the distance from the lower lip to Ricketts' line were all improved, with the P values 0.042 and 0.001, respectively. CONCLUSIONS: For patients with microgenia and hamster-like facial contour, the combination of genioplasty and autogenous external oblique line grafting is innovative and effective in improving both the front and side contour of the lower face simultaneously, with excellent stability, bone healing, and low complication rates.

Using Auricular Cartilage-fascia Composite Tissue Free Grafting Technique to Improve Cartilage Survival Outcomes.

OBJECTIVES: Auricular cartilage graft has a wide range of applications in plastic and reconstructive surgery. However, there is still a risk of absorption of the grafts over time. Intrinsic postauricular fascia (IPF) with a rich vascular network may play an important role in the nutrition and repair of auricular cartilage. This study aimed to investigate the effect of IPF on the survival viability of free auricular cartilage grafts. METHODS: 24 auricular cartilages were obtained from 6 New Zealand white rabbits which were divided into the cartilage-fascia composite graft group (FC group, n=12) and the cartilage without fascia group (C group, n=12). Two groups of cartilage were implanted into each side of the subcutaneous pocket of the rabbit's dorsum. The rabbits were sacrificed after 3 months and all cartilage grafts were obtained. Macroscopic observation, histopathological staining, and biomechanical testing were performed on all specimens. RESULTS: There were significant differences between the 2 groups regarding proliferating chondrocytes, apoptotic chondrocytes, vascularization, and matrix collagen. Compared to the auricular cartilage grafts without fascia, the auricular cartilage-fascia composite grafts had more neovascularization, proliferative chondrocytes, and type II collagen, with a homogeneous cartilage matrix and no obvious areas of heterogeneous staining. Young's modulus and ultimate tensile strength of cartilage were reduced in both groups compared to pretransplantation, but the composite graft group was superior to the fascia-free group. CONCLUSIONS: Auricular cartilage-fascial composite tissue free graft could improve cartilage survival outcomes with higher viability and mechanical properties.

Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer.

ABSTRACT: Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics.

To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-ß signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

En bloc resection of an extremely giant mediastinal immature teratoma with somatic-type malignancy: A case report with a brief review of the literature.

Primary mediastinum immature teratoma with somatic-type malignant transformation (SM) is extremely rare, and the clinical prognosis is poor. Immature teratoma with SM is difficult to eradicate by chemotherapy due to poor sensitivity; therefore, surgical resection is recommended whenever possible because it may offer better survival.

3D-CT measurements of facial symmetry in severe CFM patients: A comparative study between mandibular ascending ramus distraction osteogenesis and bone grafting.

This study aims to compare the effects of mandibular distraction osteogenesis (MDO) and bone grafting on the facial symmetry of children with Pruzansky-Kaban type IIB and III craniofacial microsomia (CFM). Medical records and three-dimensional computed tomography (3D-CT) data of CFM patients who had primarily undergone MDO and bone grafting were collected. A retrospective analysis of pre-and post-operative 3D imaging data was conducted to compare the improvement rate in facial symmetry between the two groups based on occlusal cant, affected/unaffected ramus height ratio and chin point deviation. The data were tested for normality using the Shapiro-Wilk test. When the data followed a normal distribution, a paired sample t-test was employed for the comparison between preoperative and postoperative data. When the data did not follow a normal distribution, the Wilcoxon signed-rank test for paired samples was used for preoperative and postoperative comparison. The study included 18 children with type IIB and III CFM, 11 in the MDO group and 7 in the bone grafting group. In the MDO group, postoperative Gn-FH and Gn-Cor distances increased significantly, whereas the postoperative Gn-Mid distance decreased significantly. Occlusal cant decreased significantly and ramus height affected/unaffected ratio increased significantly after MDO. In the bone graft group, there was no statistically significant difference in the postoperative ratios of chin deviation, occlusal cant, and ramus height affected/unaffected compared to the preoperative values. Compared to bone grafting, MDO can significantly enhance ramus height ratio, level occlusal plane, and centralize the chin point among patients with CFM. Furthermore, MDO achieves superior enhancements in facial symmetry.

CFL1 restores the migratory capacity of bone marrow mesenchymal stem cells in primary Sjögren's syndrome by regulating CCR1 expression.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease. There is no relevant research on whether the migratory ability of bone marrow mesenchymal stem cells (BM-MSC) is impaired in patients with pSS (pSS-BMMSC). METHODS: Trajectories and velocities of BM-MSC were analyzed. Transwell migration assay and wound healing assay were used to investigate the migratory capacity of BM-MSC. The proliferative capacity of BM-MSC was evaluated by EDU and CCK8 assay. RNA-seq analysis was then performed to identify the underlying mechanism of lentivirus-mediated cofilin-1 overexpression BM-MSC (BMMSCCFL1). The therapeutic efficacy of BMMSCCFL1 was evaluated in NOD mice. RESULTS: The migratory capacity of pSS-BMMSC was significantly reduced compared to normal volunteers (HC-BMMSC). The expression of the motility-related gene CFL1 was decreased in pSS-BMMSC. Lentivirus-mediated CFL1 overexpression of pSS-BMMSC promoted the migration capacity of pSS-BMMSC. Furthermore, RNA-seq revealed that CCR1 was the downstream target gene of CFL1. To further elucidate the mechanism of CFL1 in regulating BM-MSC migration and proliferation via the CCL5/CCR1 axis, we performed a rescue experiment using BX431 (a CCR1-specific inhibitor) to inhibit CCR1. The results showed that CCR1 inhibitors suppressed the migration and proliferation capacity of MSC induced by CFL1. CONCLUSION: The pSS-BMMSC leads to impaired migration and proliferation, and overexpression of CFL1 can rescue the functional deficiency and alleviate disease symptoms in NOD mice. Mechanically, CFL1 can regulate the expression level of the downstream CCL5/CCR1 axis to enhance the migration and proliferation of BM-MSC.

Three-dimensional Analysis of the Temporal Bone Morphology in Patients with Craniofacial Microsomia.

OBJECTIVE: To characterise the morphology of temporal bone in patients with craniofacial microsomia (CFM). DESIGN: A retrospective study. SETTING: A craniofacial centre. PATIENTS: Ninety-four patients with unilateral craniofacial microsomia. INTERVENTIONS: Mimics 21.0 (Materialise Inc., Belgium) was used to locate temporal bone landmarks on preoperative computed tomography data. The spatial Cartesian coordinate system was established in 3-matic 13.0 (Materialise Inc., Belgium). The coordinates of each landmark and the distances and angles between the landmarks were calculated. A classification system was used to quantify the severity of the zygomatic arch deformity. MAIN OUTCOME MEASURE(S): The bilateral differences in coordinates, linear and angular measurements, and the severity of temporal bone deformity (TTL δ, Psag δ, Paxiδ, and Tsag δ) among the groups were compared using the paired t-test and Kruskal-Wallis test, respectively. RESULTS: Compared to those of the unaffected side, the landmarks of the inner ear and petrous part on the affected side showed a decrease in the Z-coordinate or an increase in the X-coordinate. A superolateral rotation tendency of the temporal bone on the affected side was found. There were no significant differences in the linear and angular measurements between the groups. The degree of zygomatic arch deformation was lower in the mild group; however, no significant difference was found between the moderate and severe groups. CONCLUSIONS: In patients with CFM, asymmetry of the temporal bone and its inner organs (vestibulocochlear organ, facial nerve, and vessels) exists in multiple dimensions; its severity is not completely consistent with the degree of mandibular involvement.

Buccal Fat Pad Augmentation for Midfacial Rejuvenation: Modified Fat Grafting Technique and Ogee Line Remodeling.

BACKGROUND: The volume and position of the buccal fat pad (BFP) change with age, which manifests as a hollow midface. Previous studies showed that autologous fat grafting for BFP augmentation could effectively ameliorate midfacial hollowing. OBJECTIVES: The aim of this study was to introduce a modified fat grafting technique for female patients with midfacial hollowing to restore the volume of BFP, and to evaluate the safety and effectiveness of this approach. METHODS: Two cadavers were used for the dissection of the BFP and to demonstrate the surgical procedures. Forty-eight patients were treated for midfacial hollowing with the modified grafting strategy. The BFP was filled through a percutaneous zygomatic incision and an immediate amelioration in the hollow area was observed. Improvements were evaluated from measurements of the ogee line and ogee angle, FACE-Q questionnaires, and 3-party satisfaction ratings. Clinical profiles were reviewed and statistically analysed. RESULTS: The mean [standard deviation] ogee angle was 6.6° [1.9°] preoperatively and 3.9° [1.4°] postoperatively (average reduction, 2.7°). Patients' ogee lines were smoother postoperatively, with marked improvements in overall appearance, psychological well-being, and social confidence. Patients reported high satisfaction with decision-making and postoperative outcomes and felt 6.61 [2.21] years younger. Overall, 88%, 76%, and 83% of the cases were graded as good or excellent in improvement by surgeon, patient, and the third party, respectively. CONCLUSIONS: For age-dependent midfacial hollowing in female patients, the modified percutaneous grafting technique described here was safe and efficacious in restoring BFP volume. This technique produced a smoother ogee line and a natural, younger midfacial contour.

The prognosis and treatment of newly diagnosed bone metastasis of head and neck squamous cell cancer: an analysis of racial disparity.

OBJECTIVE: There is a lack of research investigating racial disparity in newly diagnosed head and neck squamous cell carcinoma with isolated bone metastases (HNSCC-BM). This study aims to investigate the clinical characteristics and prognostic factors in HNSCC-BM patients from different racial backgrounds to aid clinical decision making and management. METHODS: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for 345 cases of HNSCC-BM that were diagnosed between 2010 and 2017. Survival was compared using univariate and multivariate Cox proportional hazards models, Kaplan-Meier analysis, and log-rank tests. We also used propensity score matching to adjust for confounders. RESULTS: In white patients, those who were over 40 years of age had a significantly shorter survival (HR, 4.49; 95% CI 1.03-19.56; P < 0.05). Female black patients were found to survive longer compared to male patients (HR, 0.34; 95% CI 0.15-0.76; P < 0.01). Single (never married) Asians had shorter survival than married Asians (HR, 4.68; 95% CI 1.34-16.41; P < 0.05). In all three racial groups, patients who received radiotherapy in addition to chemotherapy did not survive longer than those receiving chemotherapy (P > 0.05). In Asian patients, those who underwent surgery at the primary site combined with chemoradiotherapy had significantly better survival outcomes than those who received chemoradiotherapy (HR: 0.10, 95% CI 0.01-0.88; P = 0.01). CONCLUSION: Prognostic factors differ between HNSCC-BM patients from different racial backgrounds.

Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study.

PURPOSE: This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. METHODS: A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. RESULTS: After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide and has a poor prognosis. Autophagy regulation has been proposed as a possible treatment option for HNSCC. Schisandrin B (Sch B) exerts anticancer effects by regulating apoptosis and autophagy, but the anticancer effect of Sch B in HNSCC remains unclear. This study aimed to investigate the effects of Sch B on human Cal27 HNSCC cells and to further reveal its potential regulatory mechanisms. The anticancer effect of Sch B was evaluated in vitro by flow cytometry, clonogenic assays, and Western blot analysis. The regulatory mechanism of Sch B-induced apoptosis and autophagy was further explored by polymerase chain reaction, luciferase assay, and reactive oxygen species (ROS) detection. The results showed that Sch B significantly induced apoptosis and autophagy in Cal27 cells and that inhibition of autophagy enhanced the apoptotic effect of Sch B on Cal27 cells. Additionally, Sch B-activated autophagy in Cal27 cells was dependent on the nuclear factor-kappa B (NF-κB) pathway, and ROS acted as a regulator of the NF-B pathway. N-acetylcysteine, a scavenger of ROS, inhibited Sch B-dependent autophagy via the NF-κB pathway. Based on the results, Sch B is a potential therapeutic agent for HNSCC and activates the NF-κB pathway by increasing ROS production, which subsequently promotes autophagy in HNSCC cells. Therefore, the strategy of enhancing the anticancer effect of Sch B by inhibiting autophagy deserves further attention.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. OBJECTIVE: To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. METHODS: Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. RESULTS: The preoperative pain tolerance threshold of 55 surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). CONCLUSION: The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

Primary pulmonary adenoid cystic carcinoma: A clinicopathological study of 64 patients.

BACKGROUND: This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). METHODS: Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. RESULTS: Immunohistochemical staining showed that the tumors expressed CK7, S-100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. CONCLUSION: Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.

A Novel Method for one-Stage Repair of the lip Vermilion Defects in Progressive Hemifacial Atrophy.

BACKGROUND: Progressive hemifacial atrophy often causes lip vermilion defects in patients. In this study, we described a one-stage repair method for lip defects in progressive hemifacial atrophy using a lip vermilion mucosal flap or combined dermal fat flap graft. PATIENTS AND METHODS: Patients diagnosed with progressive hemifacial atrophy with lip vermilion defects from 2010 to 2022 were included in this study. Based on the severity and location of the patient's lip defect, a lip vermilion mucosal flap was designed and transferred to the lip defect or combined with a hip dermal fat flap for one-stage repair of the lip morphology. Lip morphology and function of patients were followed up after surgery. RESULTS: A total of 22 patients were enrolled in this study, including 15 patients with lip defects on the upper lip alone and 7 patients with both upper and lower lip defects. Follow-up six months to two years postoperatively, all patients recovered uneventfully without complications. The repaired lips of the patient had a full and symmetrical morphology with no visible scarring. Two patients experienced transient dysesthesia of the lips postoperatively and both returned to normal after three months. All patients had good lip closure with normal dietary and speech function. CONCLUSIONS: The method we described for repairing lip defects in progressive hemifacial atrophy can achieve satisfactory aesthetic and functional lip results. The distinct advantage of this approach is that the patients undergo only one-stage operation and it can be used to repair both upper and lower lip defects.

IGF2BP2 acts as a m6A modification regulator in laryngeal squamous cell carcinoma through facilitating CDK6 mRNA stabilization.

Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly seen cancers in the head and neck region with increasing morbidity and mortality globally. N6-methyladenosine (m6A) modification plays a critical role in the carcinogenesis of LSCC. In this study, two datasets from online database were analyzed for differentially expressed genes (DEGs) between LSCC and normal samples. Furthermore, we carried out a series of experiments, including hematoxylin & eosin staining, immunohistochemical (IHC) staining, CCK-8, colony formation, transwell, flow cytometry, xenograft tumor model assays, actinomycin D assay, cycloheximide (CHX) assay, methylated m6A RNA immunoprecipitation (Me-RIP), RNA immunoprecipitation (RIP) assay, to verify the relevant findings in vivo and in vitro. Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was identified as an up-regulated m6A regulator in LSCC samples. Lower IGF2BP2 expression was linked to higher survival probability in LSCC and other head and neck squamous cell carcinoma patients. In LSCC cells, IGF2BP2 knockdown attenuated cancer cell aggressiveness, possibly through modulating cell cycle arrest. In the xenograft tumor model derived from IGF2BP2 knocked-down LSCC cells, IGF2BP2 knockdown inhibited tumor growth. IGF2BP2 up-regulated CDK6 expression through facilitating the stability of CDK6 mRNA and protein. CDK6 knockdown caused no changes in IGF2BP2 expression, but partially eliminated the promotive effects of IGF2BP2 overexpression on LSCC cells' aggressiveness. Overexpressed IGF2BP2 in LSCC serves as an oncogenic factor, promoting LSCC cell proliferation and invasion in vitro and tumor growth in a xenograft tumor model in vivo through facilitating CDK6 mRNA stabilization.

Bioinformatics Analysis of Hub Genes Involved in Smoke-Induced Hemifacial Microsomia Pathogenesis.

OBJECTIVE: Tobacco smoke is a recognized teratogen, which increases the risk for hemifacial microsomia (HFM) of the fetus during maternal pregnancy. The present study aimed to explore potential mechanisms and verify hub genes of HFM associated with smoke and tobacco smoke pollution (TSP) via bioinformatics methods. METHODS: Hemifacial microsomia and smoke and TSP pathogenic genes were obtained. A protein-protein interactional (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were performed by Metascape. Finally, we used the cytoHubba plug-in to screen the hub genes. RESULTS: A total of 43 HFM genes and 50 optimal smoke candidate genes were selected. Functional enrichment analysis largely focused on tissue morphogenesis and development. Two modules were identified from the PPI network, and 10 hub genes were screened out. The genes most relevant to smoke-induced HFM pathogenesis included TP53 , ESR1 , ESR2 , and HNRNPL. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of HFM related to smoke by bioinformatics analyses. Our results suggest that the TP53 , ESR1 , ESR2 , and HNRNPL gene subfamilies may have played a major role in HFM induced by smoke and TSP.

ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1.

Zinc finger CCHC-type containing 4 (ZCCHC4), RNA binding protein, has been reported to mediate rRNA methylation and affect tumor cell proliferation. However, the role of ZCCHC4 in the regulation of osteosarcoma (OS) remains unknown. ZCCHC4 was highly expressed in OS tissues and cell lines. Overexpression or silencing of ZCCHC4 promoted or inhibited cell proliferation, epithelial-mesenchymal transition (EMT), and motility. Additionally, we proved that ZCCHC4 facilitates OS progression through upregulating integrin ß1 (ITGB1). In the animal model, ZCCHC4 knockdown reduced OS tumor growth and metastases in vivo. Our findings showed that ZCCHC4 promoted the progression of OS through upregulating ITGB1 and suggested that inhibition of ZCCHC4 could be a novel therapeutic strategy for OS.

Using a New Deep Learning Method for 3D Cephalometry in Patients With Hemifacial Microsomia.

ABSTRACT: Deep learning algorithms based on automatic 3D cephalometric marking points about people without craniomaxillofacial deformities have achieved good results. However, there has been no previous report about hemifacial microsomia (HFM). The purpose of this study is to apply a new deep learning method based on a 3D point cloud graph convolutional neural network to predict and locate landmarks in patients with HFM based on the relationships between points. The authors used a PointNet++ model to investigate the automatic 3D cephalometry. And the mean distance error (MDE) of the center coordinate position and the success detection rate (SDR) were used to evaluate the accuracy of systematic labeling. A total of 135 patients were enrolled. The MDE for all 32 landmarks was 1.46 ± 1.308 mm, and 10 landmarks showed SDRs at 2 mm over 90%, and only 4 landmarks showed SDRs at 2 mm under 60%. Compared with the manual reproducibility, the standard distance deviation and coefficient of variation values for the MDE of the artificial intelligence system was 0.67 and 0.43, respectively. In summary, our training sets were derived from HFM computed tomography to achieve accurate results. The 3D cephalometry system based on the graph convolutional network algorithm may be suitable for the 3D cephalometry system in HFM cases. More accurate results may be obtained if the HFM training set is expanded in the future.