Ultrasound-Assisted miR-122-Loaded Polymeric Nanodroplets for Hepatocellular Carcinoma Gene Therapy.

Ultrasound-induced microbubble sonoporation has been shown to effectively improve drug/gene delivery efficiency by enhancing tissue and cell permeability. However, the microscale size and short duration of ultrasound contrast agents limit their accumulation in target areas. Here, a kind of ultrasound-triggered phase-transitioning and size-changing cationic nanodroplet, perfluoropentane/C9F17-PAsp(DET)/miR-122/poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets (PFP-TNDs/miR-122), was developed to deliver microRNA-122 (miR-122) for hepatocellular carcinoma (HCC) treatment. PFP served as an ultrasound-sensitive core for ultrasound-triggered phase transition and size change from the nanoscale to the microscale. Positively charged C9F17-PAsp(DET) ensured adequate miRNA loading. PGA-g-mPEG, which served as the shell of the nanodroplet, modified the nanodroplets, enhanced their stability in serum, and protected miR-122 from degradation in vivo. The results exhibited that PFP-TNDs/miR-122 has a nanosize diameter (362 ± 15 nm) and remained stable for 24 h. After treatment with PFP-TNDs/miR-122 combined with ultrasound irradiation, the miR-122 expression level was significantly increased by approximately 600-fold in HepG2 cells, 500-fold in SMMC-7721 cells, and 30-fold in human HCC xenografts. Moreover, PFP-TNDs/miR-122 combined with ultrasound radiation effectively suppressed the growth, migration, and invasion of HCC cells, and inhibited tumor proliferation in mice. This study revealed that the biodegradable PFP-TNDs is a promising therapeutic gene carrier with functions of gene protection and effective gene delivery for clinical applications. Furthermore, PFP-TNDs/miR-122 associated with ultrasound irradiation may pave a new way to improve the prognosis of patients with HCC.

Targeted Ultrasound-Triggered Phase Transition Nanodroplets for Her2-Overexpressing Breast Cancer Diagnosis and Gene Transfection.

For successful gene therapy, it is imperative to accumulate therapeutic gene in tumor tissues followed by efficiently delivering gene into targeted cells. Ultrasound irradiation, as a noninvasive and cost-effective external stimulus, has been proved to be one of the most potential external-stimulating gene delivery strategies recently in further improving gene transfection. In this study, we developed tumor-targeting ultrasound-triggered phase-transition nanodroplets AHNP-PFP-TNDs comprising a perfluorinated poly(amino acid) C11F17-PAsp (DET) as a core for simultaneously loading perfluoropentane (PFP) and nucleic acids, and a polyanionic polymer PGA-g-PEG-AHNP as the shell for not only modifying the surface of nanodroplets but also introducing an anti-Her2/neu peptide (AHNP) aiming to targeted treatment of Her2-overexpressing breast cancer. The results showed the average diameter of AHNP-PFP-TNDs was below 400 nm, nearly spherical in shape. The modification of PGA-g-PEG-AHNP not only increased the serum stability of the nanodroplets but also improved the affinity between nanodroplets and Her2-overexpressing breast cells. Both intratumor and intravenous injection of AHNP-PFP-TNDs into nude mice bearing HGC-27 xenografts showed that the gene transfection efficiency and the ultrasound contrast effect were significantly enhanced after exposed to the ultrasound irradiation with optimized ultrasound parameters. Therefore, this targeting nanodroplets system could be served as a potential theranostic vector for tumor targeting ultrasound diagnosis and gene therapy.

Novel Arch Bar Fabricated With a Computer-Aided Design and Three-Dimensional Printing: A Feasibility Study.

PURPOSE: The aim of the present study was to evaluate the feasibility of the design and fabrication of a novel arch bar using 3-dimensional printing. Furthermore, the study assessed its use in a preliminary clinical study of intermaxillary fixation. PATIENTS AND METHODS: Seven patients who met the inclusion criteria were enrolled in the present study. Plaster dental casts were created of each patient and scanned using cone-beam computed tomography to obtain digital casts. Computer-aided design software was then used to complete the virtual building of the arch bars, which were manufactured using 3-dimensional printing and a cobalt-chrome alloy. The clinical results were observed after the arch bars were fixed to the dentition with steel wires. RESULTS: The arch bar contacted the dentition with a "surface-to-surface" pattern. The utility of these novel arch bars was verified by successfully fitting them to the dental arches of the patients. All the patients achieved their desired occlusion. CONCLUSION: The results of the present study have illustrated that this digital method is feasible for constructing a novel arch bar, showing promise for clinical use.

Individualized Surgical Templates and Titanium Microplates for Le Fort I Osteotomy by Computer-Aided Design and Computer-Aided Manufacturing.

The authors report the use of novel individualized surgical templates and titanium miniplates for Le Fort I osteotomy and evaluate the accuracy of this technique in vitro. Nine three-dimensional stereolithographic skull models were used to design the templates and titanium microplates and to simulate the operation. Cone beam computed tomography (CBCT) scans of the skulls were acquired preoperatively and were used to generate virtual models. The surgical plans were made based on three-dimensional cephalometric analyses, and osteotomies were then performed virtually. Cylinder-shaped markers were placed to permit the correct location of titanium screws, and individualized surgical templates were designed. The bony segments were then repositioned virtually according to the surgical plans to correct the skeletal deformities. Resin surgical templates were produced by stereolithography rapid prototyping and the titanium miniplates by three-dimensional cutting. Le Fort I osteotomy was performed under the guide of the surgical templates and fixed with the titanium miniplates. Postoperatively, CBCT scans of each skull model were taken, and the differences between the actual and planned surgical outcomes were measured by superimposing the planned and postoperative virtual models generated from CBCT images. The authors demonstrated that the average linear difference between the planned and actual outcomes was <1 mm and the average orientation difference was <1°. The individualized surgical templates and titanium microplates designed in this experimental study permitted the repositioning of the maxillary segment to the correct planned positions during Le Fort I osteotomy, making this technique a promising alternative to the conventional split method.

Evaluation of root and alveolar bone development of unilateral osseous impacted immature maxillary central incisors after the closed-eruption technique.

INTRODUCTION: In this study, we evaluated root and alveolar bone development in unilateral osseous impacted immature maxillary central incisors by cone-beam computed tomography before and after closed-eruption treatment, in comparison with naturally erupted contralateral immature maxillary central incisors. METHODS AND RESULTS: The study included 30 patients, 20 boys and 10 girls, with a mean age of 8.44 ± 1.20 years (range, 6.5-11.2 years). After treatment, the root lengths of both the impacted maxillary central incisors (10.66 ± 2.10 mm) and the contralateral maxillary central incisors (11.04 ± 1.76 mm) were significantly greater than their pretreatment values (6.67 ± 1.94 and 9.02 ± 2.13 mm, respectively). The root canal widths of the incisors decreased significantly after treatment. From the posttreatment cone-beam computed tomography images, the ratio of exposed root length to total root length and the thickness of the alveolar bone at 1 mm under the alveolar crest and at the apex were calculated to evaluate alveolar bone development. Impacted immature maxillary central incisors differed significantly from contralateral immature maxillary central incisors in labial exposed root length, labial ratio to total root length, and lingual alveolar crest. Clinical crown height was higher (statistically but not clinically) for the impacted incisors (9.87 mm) than for the contralateral incisors (9.37 mm). CONCLUSIONS: Impacted immature incisors grew to the same stage as did erupted contralateral incisors after closed-eruption treatment. Both incisor types had some alveolar bone loss, and thin alveolar bone surrounded the roots.

[Effect of segmental Le Fort I osteotomy and bilateral sagittal split ramus osteotomy on the condyle position in skeletal class III malocclusion patients].

OBJECTIVE: To investigate the effect of segmental Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) on the condyle position in skeletal class III malocclusion patients. METHODS: In this retrospective study, 19 patients with skeletal class III malocclusion who met the inclusion criteria were enrolled. All the patients underwent the segmental Le Fort I osteotomy and BSSRO. Cone beam computed tomography (CBCT) scans were performed in the following phases: T1: within one week before the surgeries; T2: within one week post-surgery;T3:three months post-surgery; T4: 6 to 14 months post-surgery. The posterior spaces, anterior spaces and the superior spaces of the bilateral temporomandibular joints were measured according to the Kamelchuk method respectively. The fossa ratios of the condyle and the distribution of the condyle positions related to the glenoid fossa (anterior, concentric and posterior position)were calculated. The results were analyzed statistically. RESULTS: The posterior space, the anterior space and the superior space of bilateral temporomandibular joints in T2 phase[right: (2.78±1.23) mm, (2.47±0.89) mm, (3.07±0.85) mm; left: (2.93±0.83) mm, (2.69±1.14) mm, (3.44±1.16) mm] showed significantly larger spaces than those in T1 phase [right: (1.81±0.95) mm, (1.65±0.55) mm, (2.13±0.52) mm; left: (2.12± 1.05) mm, (1.79±0.59) mm, (2.15±0.93) mm],in T3 phase [right: (2.08±1.25) mm, (1.79±0.68) mm, (1.80±0.76) mm; left: (2.05±0.75) mm, (1.99±0.94) mm, (2.14±0.71) mm] and in T4 phase [right: (1.94±0.77) mm, (1.81±0.69) mm, (2.05±0.69) mm; left: (1.89±0.69) mm, (1.80±0.61) mm, (2.19±0.75) mm], P<0.05. No significant differences were observed among T1,T3 and T4 phases in the terms of the joint spaces of both sides(P>0.05).The fossa ratio and the condyle position related to the glenoid fossa had no significant difference in all the four phases (P>0.05).The results suggested that the condyle moved downward in T2 phase and changed to the original pre-surgery position in T3 phase, then keot stable in T4 phase. CONCLUSION: Segmental Le Fort I osteotomy and BSSRO caused significant and transient changes of the condyle position in skeletal class III malocclusion patients. However, the condyle tended to move back to the original pre-surgery position and might keep stable.

Sialoendoscopy-assisted sialolithectomy for submandibular hilar calculi.

PURPOSE: To assess the clinical effects of endoscopy-assisted sialolithectomy for submandibular hilar calculi. MATERIALS AND METHODS: The present study was undertaken in 70 patients with symptomatic stones in the hilum of submandibular glands who underwent endoscopy-assisted sialolithectomy from December 2005 through March 2011 in the Peking University School and Hospital of Stomatology. The operative data were analyzed retrospectively. All patients were followed periodically postoperatively. Submandibular gland function was investigated by postoperative symptoms, clinical examinations, sialography, and scintigraphy. RESULTS: Submandibular stones were successfully removed in 65 patients, with a success rate of 92.9%. Temporary lingual nerve injury occurred in 1 patient. Two patients developed ranulae and underwent an uneventful sublingual gland excision. During a mean follow-up of 23 months (range, 6 to 55 mo), 52 of 65 patients were symptom free, whereas 11 patients complained of occasional swelling of the affected gland at mealtimes and 2 patients developed a recurrent stone. Thirty patients underwent postoperative sialography. The sialographic appearances included 4 types: 1) approximately normal; 2) the main duct was significantly dilated at the hilum, but no persistent contrast was seen on the functional film; 3) the main duct was significantly dilated in the hilar region, and persistent contrast was seen at the dilated hilum of the functional film; 4) the main duct was dilated or strictured, and persistent contrast was seen on the functional film. Three of the 4 patients who underwent scintigraphy exhibited good function. CONCLUSIONS: Sialoendoscopy-assisted sialolithectomy is a safe and effective gland-preservation technique for patients with hilar stones of the Wharton's duct.

Adenomatoid odontogenic tumor with fibro-osseous reaction in the surrounding tissue.

Adenomatoid odontogenic tumor (AOT) is a relatively rare odontogenic tumor that is exclusively odontogenic epithelium in origin. We present a rare case of an AOT in a patient with fibro-osseous reaction in the surrounding tissue. A 22-year-old woman complained of gradual swelling of the right maxillary for 1 month. Radiography showed a well-defined radiolucent lesion with root resorption of the involved teeth. The biopsy revealed a primarily cystic lesion surrounded by a solid portion. Microscopically, the cystic part mainly consisted of epithelial cells organized in solid nodules, whorls, and rosettes, typically characteristic of AOT. But the surrounding solid portion showed cellular fibroconnective tissue stroma with prominent calcified spherules corresponding to ossicles and cementicles, characteristic of ossifying fibroma. The presence of a prominent fibro-osseous reaction in our case is unique. To our knowledge, these findings have not been observed in the previous reports of AOT. It could well represent a cellular cystic wall with metaplastic ossification, rather than a benign fibro-osseous neoplasm such as ossifying fibroma. The tumor had no recurrence after local resection at 5-year follow-up.

Tooth lengths of the permanent upper incisors in patients with cleft lip and palate determined with cone beam computed tomography.

Objective : To measure the tooth lengths of fully developed permanent upper incisors and to qualitatively evaluate the root shapes of the incisors in patients with cleft lip and palate (CLP). Design : Cross-sectional, noninterventional, case-control imaging study. Setting : Hospital and Stomatology Unit of Peking University, Beijing, China (institutional tertiary care). Participants : Sixty consecutive nonsyndromic CLP patients (including 40 unilateral [UCLP] and 20 bilateral [BCLP]), and 53 age- and sex-matched controls were selected for this study. Main Outcome Measure : Crown heights and root lengths of permanent upper incisors were measured from cone beam computed tomography scans, and the root shapes of upper incisors were evaluated. Results : Compared with controls, the crown heights of upper incisors in CLP patients were reduced by 9.7% to 22.5% (p < .05), and the root lengths were reduced by 15.8% to 31.7% (p < .05). BCLP patients had greater reductions than the UCLP cases (p < .05). There were no significant differences between incisors and their antimeres in controls and BCLP patients. However, measurements on the cleft side in UCLP patients were lower than those of the noncleft side (p < .05). The prevalence of atypical root shape was higher in CLP than in the control group (p  =  .002); of these, 83.3% (30/36) occurred in central incisors near the cleft. Conclusion : The permanent upper incisors in nonsyndromic CLP patients are underdeveloped. Incisor developmental deficiency was greater in teeth adjacent to the cleft.

[Quantitative assessment on artifacts of dental restorative materials in cone beam computed tomography].

OBJECTIVE: To quantitatively evaluate the artifacts appearance of eight kinds of common dental restorative materials, such as zirconia. METHODS: For the full-crown tooth preparation of mandibular first molar, eight kinds of full-crowns, such as zirconia all-ceramic crown, glass ceramic crown, ceramage crown, Au-Pt based porcelain-fused-metal (PFM) crown, Pure Titanium PFM crown, Co-Cr PFM crown, Ni-Cr PFM crown, and Au-Pd metal crown were fabricated. And natural teeth in vitro were used as controls. These full-crown and natural teeth in vitro were mounted an ultraviolet-curable resin fixed plate. High resolution cone beam computed tomography (CBCT) was used to scan all of the crowns and natural teeth in vitro, and their DICOM data were imported into software MIMICS 10.0. Then, the number of stripes and the maximum diameters of artifacts around the full-crowns were evaluated quantitatively in two-dimensional tomography images. RESULTS: In the two-dimensional tomography images,the artifacts did not appear around the natural teeth in vitro, glass ceramic crown, and ceramage crown. But thr artifacts appeared around the zirconia all-ceramic and metal crown. The number of stripes of artifacts was five to nine per one crown. The maximum diameters of the artifacts were 2.4 to 2.6 cm and 2.2 to 2.7 cm. CONCLUSION: In the two-dimensional tomography images of CBCT, stripe-like and radical artifacts were caused around the zirconia all-ceramic crown and metal based porcelain-fused-metal crowns. These artifacts could lower the imaging quality of the full crown shape greatly. The artifact was not caused around the natural teeth in vitro, glass ceramic crown, and ceramage crown.

Multifunctional polysaccharide composited microneedle for oral ulcers healing.

Oral ulcers have periodicity and recurrence, and the etiology and causative mechanisms remain unclear; therefore, it is difficult to treat oral ulcers effectively. Current clinical treatment methods mainly include pain relief and administration of anti-inflammatories to prevent secondary infections and a prolonged recurrence cycle. However, these traditional treatment methods are administered independently and are susceptible to muscle movements and constant salivary secretion in the mouth, resulting in ineffective drug functioning. Therefore, development of a novel treatment to reduce wound infection and accelerate wound healing for oral ulcers is required for effective treatment. Herein, we report a multifunctional polysaccharide composite microneedle patch based on hyaluronic acid (HA) and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) loaded with dexamethasone (DXMS) and basic fibroblast growth factor (bFGF) for oral ulcer healing. DXMS and bFGF encapsulated the HA tip portion of the microneedle patch, endowing the microneedle patches with anti-inflammatory and angiogenic properties. HACC was applied to the back of the microneedle patch, adding antibacterial properties. The experimental results indicated that the prepared dressings exhibited good antibacterial activity and effectively promoted cell migration growth and angiogenesis. More importantly, animal experiments have shown that multifunctional microneedle patches can effectively promote oral ulcer healing. Thus, these novel multifunctional polysaccharide composite microneedle patches have great potential for oral ulcers treatment.

[Diagnostic accuracy of cone beam computed tomography and eight-slice computed tomography for evaluation of external root reabsorption].

OBJECTIVE: To evaluate the diagnostic accuracy of cone beam computed tomography (CBCT) and high resolution multi-slice computed tomography (MSCT) with eight-detector-rows in detecting the simulated external root resorption defects. METHODS: External root resorption defects of different sizes and in different locations were simulated in 40 human single rooted teeth. Cavities simulating root resorption defects of 1 mm in diameter and 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm in depth were drilled in the cervical, middle and apical thirds of lingual surfaces of the teeth. The specimens were scanned with both CBCT (Accuitomo 3DX, Morita Co., Japan) and high resolution 8-slice CT (BrightSpeed Edge, GE Co., USA). The CBCT and MSCT images were read by two experienced observers. The data were analyzed with receiver operating characteristics (ROC) analysis. ROC curves were generated and the area under ROC curve (Az) was employed to express the diagnostic accuracy. RESULTS: The diagnostic accuracy (Az value) in detecting the simulated defects of all the locations and sizes were 0.921 for CBCT and 0.770 for MSCT. The Az values for CBCT in detecting defects located in the cervical, middle and apical thirds were 0.885, 0.991 and 0.873, while those for MSCT were 0.752, 0.844 and 0.709, respectively. The Az values for CBCT in detecting the defects of 0.1 mm, 0.2 mm, 0.3 mm and 0.4 mm in depth were 0.794, 0.934, 0.992 and 0.992, and those for MSCT were 0.592, 0.719, 0.920 and 0.990, respectively. CONCLUSION: The diagnostic ability for external root resorption of CBCT is better than that of MSCT. Smaller defects are better delineated with CBCT than with MSCT. The defects in the middle thirds of the roots are easier to be detected than those in the cervical and apical ones using both CBCT and MSCT.

Should the solid variant of odontogenic keratocyst and keratoameloblastoma be classified as the same entity? A clinicopathological analysis of nine cases and a review of the literature.

The solid variant of odontogenic keratocyst (SOKC) is an extremely rare odontogenic lesion, which remains poorly defined even in the 2017 World Health Organization odontogenic tumour classification. It is difficult to distinguish between SOKC and so called keratoameloblastoma (KAB), both rare lesions that have similarities in clinical, histological and biological characteristics. Here, we report clinicopathological data and results of molecular analysis of nine cases with a literature review. First, they were compared to previously reported cases of SOKC and/or KAB, and many overlaps were found in clinical and pathological characteristics. Second, we performed PCR analysis for BRAF V600E mutation. Although ameloblastoma-like epithelia were often encountered, none exhibited BRAF V600E mutation, which has been reported to occur frequently in ameloblastomas but not in odontogenic keratocysts (OKCs). One of two cases of SOKC in the present series from which fresh frozen tissue specimens were available was found to harbour PTCH1 mutations, indicating that these were more likely to be a subtype of OKC. Moreover, we also examined the differences between SOKC and primary intraosseous carcinoma (PIOC) with regard to the expression of cytokeratins (pan-CK, CK5/6, CK7, CK8/18, CK10, CK14 and CK19), p53 and Ki-67. The proportions of p53-and Ki-67-positive cells were significantly higher in PIOC than in SOKC. These findings suggest that immunostaining for p53 and Ki-67 would be useful to differentiate between SOKC and PIOC. We also conducted a review of SOKC and KAB cases reported in the English language literature.

Modulation of Tumor Hypoxia by pH-Responsive Liposomes to Inhibit Mitochondrial Respiration for Enhancing Sonodynamic Therapy.

BACKGROUND AND PURPOSE: Sonodynamic therapy (SDT) has been widely used for the noninvasive treatment of solid tumors, but the hypoxic tumor microenvironment limits its therapeutic effect. The current methods of reoxygenation to enhance SDT have limitations, prompting reconsideration of the design of therapeutic approaches. Here, we developed a tumor microenvironment-responsive nanoplatform by reducing oxygen consumption to overcome hypoxia-induced resistance to cancer therapy. METHODS: A pH-responsive drug-loaded liposome (MI-PEOz-lip) was prepared and used to reduce oxygen consumption, attenuating hypoxia-induced resistance to SDT and thereby improving therapeutic efficiency. Photoacoustic imaging (PAI) and fluorescence imaging (FI) of MI-PEOz-lip were evaluated in vitro and in breast xenograft tumor models. The pH-sensitive functionality of MI-PEOz-lip was applied for pH-triggered cargo release, and its capacity was evaluated. The MI-PEOz-lip-mediated SDT effect was compared with other treatments in vivo. RESULTS: MI-PEOz-lip was demonstrated to specifically accumulate in tumors. Metformin molecules in liposomes selectively accumulate in tumors by pH-responsive drug release to inhibit the mitochondrial respiratory chain while releasing IR780 to the tumor area. These pH-responsive liposomes demonstrated PAI and FI imaging capabilities in vitro and in vivo, providing potential for treatment guidance and monitoring. In particular, the prepared MI-PEOz-lip combined with ultrasound irradiation effectively inhibited breast tumors by producing toxic reactive singlet oxygen species (ROS), while the introduction of metformin inhibited mitochondrial respiration and reduced tumor oxygen consumption, resulting in excellent sonodynamic therapy performance compared with other treatments. CONCLUSION: In this study, we present a novel strategy to achieve high therapeutic efficacy of SDT by the rational design of multifunctional nanoplatforms. This work provides a new strategy that can solve the current problems of inefficient oxygen delivery strategies and weaken resistance to various oxygen-dependent therapies.

Treatment strategy of hilar and intraglandular stones in wharton's duct: A 12-year experience.

OBJECTIVES/HYPOTHESIS: To suggest a strategy for transoral removal of hilar and intraparenchymal submandibular stones. STUDY DESIGN: Retrospective case series. METHODS: Retrospective evaluation was performed for 514 consecutive patients with hilar and intraparenchymal submandibular stones treated via endoscopy-assisted surgery from January 2006 to June 2018. Three patients had bilateral stones. The stones were classified as: hilar (type I), posthilar (type II), intraparenchymal (type III), and multiple stones (type IV). RESULTS: The affected glands included 311 with type I, 84 with type II, 65 with type III, and 57 with type IV stones. Stones were successfully removed in 478 glands (92.5%, 478/517). Main treatment techniques included hilum ductotomy in 311 glands, intraparenchymal ductotomy in 68, submandibulotomy in 14, intraductal retrieval in 74, and hilum ductotomy accompanied by intraductal retrieval in 11. At a mean 40-months follow-up of 478 successful cases, clinical outcomes were good in 425, fair in 27, and poor in 26 glands. Postoperative sialograms in 75 stone-free patients were categorized as: type I, normal (n = 6); type II, ectasia or stenosis in the main duct and no persistent contrast on functional films (n = 44); type III, ectasia or stenosis in the main duct and mild contrast retention (n = 15); and type IV, poor shape of the main duct and evident contrast retention (n = 10). Postoperative sialometry of 32 patients revealed no significant differences of the gland function between the two sides. CONCLUSIONS: Appropriate use of various endoscopy-assisted approaches helps preserve the gland and facilitates recovery of gland function in patients with different depths of hilo-parenchymal submandibular stones. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2360-2365, 2020.

Ultrasound triggered phase-change nanodroplets for doxorubicin prodrug delivery and ultrasound diagnosis: An in vitro study.

Ultrasound-triggered delivery system is among the various multifunctional and stimuli-responsive strategies that hold great potential as a robust solution to the challenges of localized drug delivery and gene therapy. In this work, we developed an ultrasound-triggered delivery system PFP/C9F17-PAsp(DET)/CAD/PGA-g-mPEG nanodroplet, which combined ultrasound responsive phase-change contrast agent, acid-cleavable doxorubicin prodrug and cationic amphiphilic fluorinated polymer carrier, aiming to achieve both high imaging contrast and preferable ultrasound-triggered anti-cancer therapeutic effect. The optimized nanodroplets were characterized as monodispersed particles with a diameter of about 400 nm, slightly positive surface charge and high drug-loading efficiency. The functional augmenter PGA-g-mPEG provided the nanodroplets good sustainability, low cytotoxicity and good serum compatibility, as confirmed by stability and biocompatibility tests. In ultrasound imaging study, the nanodroplets produced significant contrast with ultrasound irradiation (3.5 MHz, MI = 0.08) at 37 ℃. Cell uptake and cytotoxicity studies in HepG2 and CT-26 cells showed the enhanced drug uptake and therapeutic effect with the combination of nanodroplets and ultrasound irradiation. These results suggest that the PFP/CAD-loaded phase change nano-emulsion can be utilized as an efficient theranostic agent for both ultrasound contrast imaging and drug delivery.

Computer-aided autotransplantation of teeth with 3D printed surgical guides and arch bar: a preliminary experience.

BACKGROUND/AIM: Autotransplantation of teeth is a method to restore the missing teeth and computer-aided techniques have been applied in this field. The aim of this study was to describe a novel approach for computer-aided autotransplantation of teeth and to preliminarily assess its feasibility, accuracy, and stability. METHODS: Eight wisdom teeth with complete root formation of eight adult patients were autotransplanted. Individual replicas of donor teeth with local splints, surgical templates, and arch bars were virtually designed and fabricated using three-dimensional printing, these were then applied in the autotransplantation surgeries. Clinical and radiological outcomes were observed, the extra-alveolar time, success rate, and 1-year survival rate were analyzed, and accuracy and stability of this approach were evaluated. RESULTS: The extra-alveolar time of donor teeth were less than 3 min. The average follow-up duration was 2.00 ± 1.06 years. All autotransplanted teeth showed normal masticatory function. Ankylosis was found in one patient, and the overall success rate was 87.5%, whereas the 1-year survival rate was 100%. Linear differences between the designed and the immediate autotransplanted positions at crowns and apexes of the donor teeth were 1.43 ± 0.57 and 1.77 ± 0.67 mm, respectively. Linear differences between immediate and the stable positions at crowns and apexes of the donor teeth were 0.66 ± 0.36 and 0.67 ± 0.48 mm, respectively. CONCLUSION: The present study illustrated the feasibility, clinical satisfied accuracy, and stability of a novel approach for computer-aided autotransplantation of teeth. This new approach facilitated the surgical procedure and might be a viable and predictable method for autotransplantation of teeth.

Evaluation of trabecular structure changes in osteoarthritis of the temporomandibular joint with cone beam computed tomography imaging.

OBJECTIVES: To explore the possibility of using 2-dimensional image assessments in combination with cone beam computed tomography (CBCT) in patients with temporomandibular joint osteoarthritis (TMJOA) to enhance the clinical significance and applicability of the CBCT findings on TMJOA changes. STUDY DESIGN: Fifty-two patients with unilateral TMJOA and 40 healthy adults who had undergone CBCT in preparation for orthodontic treatment were selected for this study. Temporomandibular joint images were acquired with CBCT. All images were classified into 4 phases (slight erosion, widespread erosion, appearance of bone maintenance, and partial loss of condylar head with a remodeled cortical surface) and 4 levels of severity (absent, slight, moderate, and extensive). Quantitative microstructural analysis, including bone value fraction (BV/TV), trabecular number (Tb.N), trabecular thickness, and trabecular separation (Tb.Sp) of each image, was performed by using a customized software. RESULTS: In patients with unilateral TMJOA, the affected side had significantly higher BV/TV and Tb.N and significantly lower Tb.Sp compared with the unaffected side. Compared with healthy individuals, the affected joints in patients with TMJOA had significantly higher BV/TV and trabecular thickness and significantly lower Tb.N and Tb.Sp. No significant difference was found among different phase groups or different severity levels. CONCLUSIONS: CBCT combined with a software investigation protocol for microstructure measurement can be used to provide reliable trabecular parameters in assessing TMJOA.

[Endoscopy-assisted sialolithectomy for the calculus of the Stensen's duct].

OBJECTIVE: To investigate the clinical effects of endoscopy-assisted sialolithectomy for the calculus in the Stensen's duct. METHODS: From August 2005 to July 2013, 67 consecutive patients with calculus (or foreign bodies) in the Stensen's duct underwent explorative and interventional endoscopy in our hospital. The stones (or foreign bodies) were removed by endoscopy-assisted technique. After operation, the patients were followed-up periodically, and treatment effects were analyzed. RESULTS: Among the 67 patients, the stones (or foreign bodies) were completely removed in 58 cases, and almost completely removed in 3 cases, with a success rate of 87% (58/67). Among the 61 stone-removed cases, treatment options included direct removal with aid of basket or forceps (24 cases), basket entrapment and opening-up of the ostium (21 cases), basket entrapment and mucosal incision near the ostium (8 cases), open removal via buccal incision (2 cases) and open removal via pre-auricular flap (6 cases). During the 6-90 months' follow-up of the 61 cases, 48 cases were asymptomatic, 7 had mild symptoms, 3 developed ductal obturation, 1 had numbness in the parotid region, and the remaining 2 were missed. CONCLUSIONS: Endoscopy-assisted sialolithectomy is a safe and effective gland-preservation technique for the patients with parotid gland calculus.

Stable cerasomes for simultaneous drug delivery and magnetic resonance imaging.

Magnetic liposomes have been frequently used as nanocarriers for targeted drug delivery and magnetic resonance imaging in recent years. Despite great potentials, their morphological/structural instability in the physiological environment still remains an intractable challenge for clinical applications. In this study, stable hybrid liposomal cerasomes (ie, liposomes partially coated with silica) which can co-encapsulate Fe3O4 nanoparticles and the anticancer drug paclitaxel were developed using thin film hydration method. Compared with the drug loaded liposomes, the paclitaxel-loaded magnetic cerasomes (PLMCs) exhibited much higher storage stability and better sustained release behavior. Cellular uptake study showed that the utilization of an external magnetic field significantly facilitated the internalization of PLMCs into cancer cells, resulting in potentiated drug efficacy of killing tumor cells. The T2 relaxivity (r2) of our PLMCs was much higher than that of free Fe3O4 nanoparticles, suggesting increased sensitivity in T2-weighted imaging. Given its excellent biocompatibility also shown in the study, such dual functional PLMC is potentially a promising nanosystem for effective cancer diagnosis and therapy.