Evaluation of thiadiazine-based PET radioligands for imaging the AMPA receptor.

As a subclass of ionotropic glutamate receptors (iGluRs), α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been implicated in various neurological disorders and neurodegenerative diseases. To further our understanding of AMPA receptor-related disorders in the central nervous system (CNS), it is important to be able to image and quantify AMPA receptors in vivo. In this study, we identified a novel F-containing AMPA positive allosteric modulator (PAM) 6 as a potential lead compound. Molecular docking studies and CNS PET multi-parameter optimization (MPO) analysis were used to predict the absorption, distribution, metabolism, and excretion (ADME) characteristics of 6 as a PET probe. The resulting PET probe, [18F]6 (codename [18F]AMPA-2109), was successfully radiolabeled and demonstrated excellent blood-brain barrier (BBB) permeability and high brain uptake in rodents and non-human primates. However, [18F]6 did not show substantial specific binding in the rodent or non-human primate brain. Further medicinal chemistry efforts are necessary to improve specific binding, and our work may serve as a starting point for the design of novel 18F-labeled AMPA receptor-targeted PET radioligands aimed for clinical translation.

Novel 3D-printing bilayer GelMA-based hydrogel containing BP,ß-TCP and exosomes for cartilage-bone integrated repair.

The integrated repair of cartilage and bone involves the migration and differentiation of cells, which has always been a difficult problem to be solved. We utilize the natural biomaterial gelatin to construct gelatin methacryloyl (GelMA), a hydrogel scaffold with high cell affinity. GelMA is mixed with different components to print a bi-layer porous hydrogel scaffold with different modulus and composition in upper and lower layers through three-dimensional (3D) printing technology. The upper scaffold adds black phosphorus (BP) and human umbilical cord mesenchymal stem cells (hUMSCs) exosomes (exos) in GelMA, which has a relatively lower elastic modulus and is conducive to the differentiation of BMSCs into cartilage. In the lower scaffold, in addition to BP and hUMSCs exos,ß-tricalcium phosphate (ß-TCP), which has osteoconductive and osteoinductive effects, is added to GelMA. The addition ofß-TCP significantly enhances the elastic modulus of the hydrogel scaffold, which is conducive to the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In vitroexperiments have confirmed that the bi-layer scaffolds can promote osteogenesis and chondrogenic differentiation respectively. And in the rabbit cartilage-bone injury model, MRI and micro-CT results show that the 3D printed bi-layer GelMA composite scaffold has a repair effect close to normal tissue.

Research status of facial nerve repair.

The facial nerve, also known as the seventh cranial nerve, is critical in controlling the movement of the facial muscles. It is responsible for all facial expressions, such as smiling, frowning, and moving the eyebrows. However, damage to this nerve can occur for a variety of reasons, including maxillofacial surgery, trauma, tumors, and infections. Facial nerve injuries can cause severe functional impairment and can lead to different degrees of facial paralysis, significantly affecting the quality of life of patients. Over the past ten years, significant progress has been made in the field of facial nerve repair. Different approaches, including direct suture, autologous nerve grafts, and tissue engineering, have been utilized for the repair of facial nerve injury. This article mainly summarizes the clinical methods and basic research progress of facial nerve repair in the past ten years.

Application of a Lateral Pedicled Cranial Bone Flap for the Treatment of Secondary Zygomaticomaxillary Defects.

This study aimed to evaluate the effect of laterally-based pedicled cranial bone flap (LBPCBF) for the repair of secondary zygomaticomaxillary defects. Between December 2014 and December 2016, 6 patients with unilateral zygomaticomaxillary defects were selected; of these, 5 had trauma, and 1 was exposed to titanium mesh in the infraorbital area due to radiotherapy following total maxillectomy for right maxillary squamous cell carcinoma. Preoperatively, 3 patients suffered from an intraoral vestibular groove fistula, 2 suffered from an extraoral fistula, and 1 from local exposure of titanium mesh. Surgical treatment was implemented in all 6 patients, of which, the 5 trauma patients underwent debridement, reduction, and fixation of periorbital fracture, followed by repair of the defects in the infraorbital margin, anterior wall of maxillary sinus, and zygomatic body with LBPCBF, and then, reconstruction of the orbital floor with titanium mesh. The other patient with exposed titanium mesh underwent repair of defects in the infraorbital margin and anterior wall of the maxillary sinus with LBPCBF after titanium mesh trimming. Postoperative review at 6 months revealed disappearance of intraoral fistula, wound healing, and improvement of facial deformity in all 6 patients, of which 2 patients demonstrated postoperative ectropion. The application of LBPCBF can simultaneously repair bone defects in the infraorbital margin, anterior wall of maxillary sinus, and zygomatic body, as well as, supplement the soft tissue, thereby indicating a satisfactory treatment effect.

Arglabin is a plant sesquiterpene lactone that exerts potent anticancer effects on human oral squamous cancer cells via mitochondrial apoptosis and downregulation of the mTOR/PI3K/Akt signaling pathway to inhibit tumor growth in vivo.

PURPOSE: To evaluate the anticancer effects and the underlying mechanism of arglabin on oral squamous cell carcinoma (OSCC) cells. METHODS: 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) and annexin V/propidium iodide (PI) staining were performed to evaluate apoptosis. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were examined by flow cytometry. Protein expression was assessed by western blot analysis. To examine the anticancer activity of arglabin in vivo, subcutaneous xenografts in nude mice were evaluated. RESULTS: Arglabin exhibited an IC50 of 10 µM in OSCC cells and induced apoptosis by inhibiting MMP and enhancing intracellular ROS levels. DAPI and annexin V/PI staining indicated apoptosis of OSCC cells induced by arglabin. Arglabin also downregulated the expression of key proteins in the mTOR/PI3K/Akt signaling pathway. In vivo evaluation showed that arglabin reduced the average tumor volumes and growth of xenografted tumors, indicative of its anticancer activity. CONCLUSIONS: Arglabin showed selective in vitro and in vivo anticancer activities against OSCC cells and is therefore a potential therapeutic agent for the management of OSCC.

Traumatic dental injuries among 8- to 12-year-old schoolchildren in Pinggu District, Beijing, China, during 2012.

BACKGROUND: Although traumatic dental injuries are most common during childhood and can cause significant health problems, the literature contains few reports of the prevalence of traumatic dental injuries in children in China. AIM: To study the prevalence of and factors related to traumatic dental injuries among 8- to 12-year-old schoolchildren in Pinggu District, Beijing during 2012. MATERIAL AND METHODS: An epidemiological survey of traumatic dental injuries was performed in all nine primary schools of Pinggu District, Beijing, China. Andreasen criteria as the diagnostic criteria were used in the study. A sample of 5165 students aged from 8 to 12 years old were examined, consisting of 2711 boys and 2454 girls. RESULTS: A total of 367 students (7.1%), 251 boys and 116 girls, were found to have traumatic dental injuries, and 442 permanent teeth were involved. Maxillary central incisors were the most affected by dental injuries (378, 85.5%). Among the 52 traumatized teeth (11.8%) that were treated, endodontic treatment (55.8%) was the most common method. CONCLUSIONS: The study showed a relatively low prevalence of dental injuries in Pinggu District. The treatment rate of traumatized teeth was relatively low. Schoolchildren need more medical assistance when they face accidents. Policymakers should develop a strategy for the prevention of traumatic dental injuries. Educational programs to increase the knowledge of traumatic dental injuries and prevent them should be initiated for teachers and schoolchildren.

[Correction of enophthalmos following orbital fracture with computer-assisted navigation system].

OBJECTIVE: To evaluate the efficiency of individually fabricated titanium mesh to correct enophthalmos following orbital fracture by using computer-assisted navigation system. METHODS: Forty- nine patients with unilateral orbital fracture were divided into navigation group (25 cases) and non-navigation group (24 cases). All patients underwent orbital reconstruction to correct post-traumatic enophthalmos with individually fabricated titanium mesh. The bilateral global projection and the orbital volumn were measured preoperatively and postoperatively. The depth of titanium mesh was measured postoperatively. RESULTS: Statistical analysis demonstrated the global projection at the affected side increased by (3.35 ± 1.46) mm in navigation group and by (2.25 ± 1.14) mm in non- navigation group postoperatively, and there was a significant difference between the two groups (P < 0.05). The orbital volumn at the affected side decreased by (5.94 ± 2.20) ml in navigation group and by (4.21 ± 2.18) ml in non-navigation group, and there was a significant difference between the two groups (P < 0.05). The depth of titanium was (31.95±2.97) mm in navigation group and (29.27±2.72) mm in non-navigation group, and the values between the two groups differed significantly (P < 0.05). CONCLUSIONS: The use of computer-assisted navigation for the orbital wall reconstruction with individually fabricated titanium mesh can protect the optic nerve reliably and achieve satisfactory results.