Biomimetic Nano-Cancer Stem Cell Scavenger for Inhibition of Breast Cancer Recurrence and Metastasis after FLASH-Radiotherapy.

Compared to conventional radiotherapy (RT), FLASH-RT delivers ultra-high dose radiation, significantly reducing damage to normal tissue while guaranteeing the effect of cancer treatment. However, cancer recurrence and metastasis frequently occur after all RT due to the existence of intractable cancer stem cells (CSCs). To address this, a biomimetic nanoplatform (named TAFL) of tumor-derived exosome fusion liposomes is designed by co-loading aggregation-induced emission photothermal agents, TPE-BBT, and anti-cancer drugs, aspirin, aiming to clear CSCs for inhibiting cancer recurrence and metastasis after FLASH-RT therapy . Aspirin released in TAFL system triggered by laser irradiation can induce apoptosis and DNA damage of 4T1 CSCs, comprehensively downregulate their stemness phenotype, and inhibit their sphericity. Furthermore, the TPE-BBT mediated mild-photothermal therapy can alleviate the hypoxic tumor microenvironment, inhibit the DNA repair of CSCs, which further amplifies the effect of aspirin against CSCs, therefore reduces the effective dose of aspirin, making TAFL more biologically safe. In vivo experimental results demonstrated that decreased CSCs population mediated by TAFL system treatment significantly inhibited tumor recurrence and metastasis after FLASH-RT therapy. In summary, this TAFL system   provides a new idea for the future clinical application of FLASH-RT therapy.

Automatic classification and segmentation of multiclass jaw lesions in cone-beam CT using deep learning.

OBJECTIVES: To develop and validate a modified deep learning (DL) model based on nnU-Net for classifying and segmenting five-class jaw lesions using cone-beam CT (CBCT). METHODS: A total of 368 CBCT scans (37 168 slices) were used to train a multi-class segmentation model. The data underwent manual annotation by two oral and maxillofacial surgeons (OMSs) to serve as ground truth. Sensitivity, specificity, precision, F1-score, and accuracy were used to evaluate the classification ability of the model and doctors, with or without artificial intelligence assistance. The dice similarity coefficient (DSC), average symmetric surface distance (ASSD), and segmentation time were used to evaluate the segmentation effect of the model. RESULTS: The model achieved the dual task of classifying and segmenting jaw lesions in CBCT. For classification, the sensitivity, specificity, precision, and accuracy of the model were 0.871, 0.974, 0.874, and 0.891, respectively, surpassing oral and maxillofacial radiologists (OMFRs) and OMSs, approaching the specialist. With the model's assistance, the classification performance of OMFRs and OMSs improved, particularly for odontogenic keratocyst (OKC) and ameloblastoma (AM), with F1-score improvements ranging from 6.2% to 12.7%. For segmentation, the DSC was 87.2% and the ASSD was 1.359 mm. The model's average segmentation time was 40 ± 9.9 s, contrasting with 25 ± 7.2 min for OMSs. CONCLUSIONS: The proposed DL model accurately and efficiently classified and segmented five classes of jaw lesions using CBCT. In addition, it could assist doctors in improving classification accuracy and segmentation efficiency, particularly in distinguishing confusing lesions (eg, AM and OKC).

Characterization of VvmiR166s-Target Modules and Their Interaction Pathways in Modulation of Gibberellic-Acid-Induced Grape Seedless Berries.

Exogenous GA is widely used to efficiently induce grape seedless berry development for significantly improving berry quality. Recently, we found that VvmiR166s are important regulators of response to GA in grapes, but its roles in GA-induced seedless grape berry development remain elusive. Here, the precise sequences of VvmiR166s and their targets VvREV, VvHB15 and VvHOX32 were determined in grape cv. 'Rosario Bianco', and the cleavage interactions of VvmiR166s-VvHB15/VvHOX32/VvREV modules and the variations in their cleavage roles were confirmed in grape berries. Exogenous GA treatment significantly induced a change in their expression correlations from positive to negative between VvmiR166s and their target genes at the seeds during the stone-hardening stages (32 DAF-46 DAF) in grape berries, indicating exogenous GA change action modes of VvmiR166s on their targets in this process, in which exogenous GA mainly enhanced the negative regulatory roles of VvmiR166s on VvHB15 among all three VvmiR166s-target pairs. The transient OE-VvmiR166a-h/OE-VvHB15 in tobacco confirmed that out of the VvmiR166 family, VvmiR166h/a/b might be the main factors in modulating lignin synthesis through inhibiting VvHB15, of which VvmiR166h-VvHB15-NtPAL4/NtCCR1/NtCCR2/NtCCoAMT5/NtCOMT1 and VvmiR166a/b-VvHB15-NtCAD1 are the potential key regulatory modules in lignin synthesis. Together with the GA-induced expression modes of VvmiR166s-VvHB15 and genes related to lignin synthesis in grape berries, we revealed that GA might repress lignin synthesis mainly by repressing VvCAD1/VvCCR2/VvPAL2/VvPAL3/Vv4CL/VvLac7 levels via mediating VvmiR166s-VvHB15 modules in GA-induced grape seedless berries. Our findings present a novel insight into the roles of VvmiR66s that are responsive to GA in repressing the lignin synthesis of grape seedless berries, with different lignin-synthesis-enzyme-dependent action pathways in diverse plants, which have important implications for the molecular breeding of high-quality seedless grape berries.

Oral and maxillofacial emergencies: A retrospective study of 5220 cases in West China.

BACKGROUND/AIM: There are no epidemiological reports focused on the oral and maxillofacial surgery emergency department in the West China Hospital of Stomatology. The aim of this study was to analyse the epidemiological characteristics of emergency patients admitted for Trauma and Plastic Surgery Department of the West China Hospital of Stomatology from 2016-2019. MATERIALS AND METHODS: In this retrospective study, 5220 patients with complete medical records were evaluated. The following data were collected: gender, age, etiology, disease type distribution, anatomic injury site and treatment modality. RESULTS: There were 3046 males and 2174 females (ratio 1.40:1), with an average age of 16.2 years. The largest group was children aged between 3 and 6 years old (28.3%). Maxillofacial injuries were the most common condition (87.3%), which mostly occurred on the forehead (29.7%), followed by the lips (27.8%). A fall was the leading cause of injury (59.9%), especially in patients younger than 6 years old. There were 327 cases of maxillofacial space infections (MSI), and the mandibular third molars were the most common tooth associated with odontogenic infections (36.2%). Univariable analysis identified that multiple-space infection, visit time and systemic conditions were the risk factors for being admitted to the hospital for treatment. There were 116 patients (2.2%) with bleeding as the main complaint, and most of the maxillofacial bleeding patients could be stopped by compression (52.6%). CONCLUSION: Males and children aged younger than 6 years were the highest risk populations. Trauma accounted for the majority of emergency patients in maxillofacial surgery. Most maxillofacial injuries involved the forehead and were mainly caused by accidental falls. The proportion of MSI was not high, but serious cases may be life-threatening. The causes of bleeding were diverse, and the bleeding was easy to control.

Recent advance in technological innovations of sugar-reduced products.

Sugar is crucial as an essential nutrient for humans as well as for providing texture, sweetness and so on to food. But with the rise in people's pursuit of health, it is becoming increasingly clear that excessive consumption of sugar can locate a load on the body. It has been that excessive sugar is associated with many diseases, such as dental caries, obesity, diabetes, and coronary heart disease. Therefore, researchers and industries are trying to reduce or substitute sugar in food without affecting the sensory evaluation. Substituting sugar with sweeteners is alternatively becoming the most traditional way to minimize its use. So far, the sweeteners such as stevia and xylitol have been are commercially applied. Several studies have shown that technological innovation can partially compensate for the loss in sweetness as a result of sugar reduction, such as cross-modal interactions that stimulate sweetness with aroma, nanofiltration that filters disaccharides and above, enzyme-catalyzed sugar hydrolysis, and microbial fermentation that turns sugar into sugar alcohol. This review summarizes these studies to enhance the safety and quality of sugar-reduced products, and will provide some theoretical frameworks for the food industry to reduce sugar in foods, meet consumers' needs, and promote human health.

A bright chemiluminescence conjugated polymer-mesoporous silica nanoprobe for imaging of colonic tumors in vivo.

Hypochlorite acid (ClO-) is one of the major reactive oxygen species (ROS) in colon cancer, providing an effective target for colonic tumor in vivo imaging. For detection of ClO- and tumor imaging, poly[(9,9-di(2-ethylhexyl)-9H-fluorene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PFV-co-MEHPV, namely CP1) was encapsulated in mesoporous silica nanoparticles (MSNs) that were pre-modified with polyphenylenevinylene (PPV) via in situ polymerization to construct bright PPV@MSN-CP1 nanoparticles. The synthesized nanoparticles were size-stable and not cytotoxic as confirmed by FE-TEM, FE-SEM, and MTT assay. Hypochlorite oxidizes the vinylidene bond of CP1 through π2-π2 cycloaddition to form PPV-dioxetane intermediates to generate photons. The CL quantum yield of PPV@MSN-CP1 was 16.7 times higher than that of Pluronic F-127 wrapped CP1. CL nanoparticles PPV@MSN-CP1 have good selectivity for hypochlorite detection among biological oxidants (mainly ROS). The linear range and the LOD of PPV@MSN@CP1 for ClO- detection are 4-90 and 1.02 µM, respectively. Subsequently, we further coated PPV@MSN@CP1 with folic acid for tumor targeting by phospholipid wrapping. PPV@MSN-CP1@FA was successfully applied for in vivo imaging of endogenously produced ClO- of tumor tissue in living animals.

Intelligent Pore Switch of Hollow Mesoporous Organosilica Nanoparticles for High Contrast Magnetic Resonance Imaging and Tumor-Specific Chemotherapy.

Hollow mesoporous organosilica nanoparticles (HMONs) are widely considered as a promising drug nanocarrier, but the loaded drugs can easily leak from HMONs, resulting in the considerably decreased drug loading capacity and increased biosafety risk. This study reports the smart use of core/shell Fe3O4/Gd2O3 (FG) hybrid nanoparticles as a gatekeeper to block the pores of HMONs, which can yield an unreported large loading content (up to 20.4%) of DOX. The conjugation of RGD dimer (R2) onto the DOX-loaded HMON with FG capping (D@HMON@FG@R2) allowed for active tumor-targeted delivery. The aggregated FG in D@HMON@FG@R2 could darken the normal tissue surrounding the tumor due to the high r2 value (253.7 mM-1 s-1) and high r2/r1 ratio (19.13), and the intratumorally released FG as a result of reducibility-triggered HMON degradation could brighten the tumor because of the high r1 value (20.1 mM-1 s-1) and low r2/r1 ratio (7.01), which contributed to high contrast magnetic resonance imaging (MRI) for guiding highly efficient tumor-specific DOX release and chemotherapy.

Automatic localization of cephalometric landmarks based on convolutional neural network.

INTRODUCTION: Cephalometry plays an important role in the diagnosis and treatment of orthodontics and orthognathic surgery. This study intends to develop an automatic landmark location system to make cephalometry more convenient. METHODS: In this study, 512 lateral cephalograms were collected, and 37 landmarks were included. The coordinates of all landmarks in the 512 films were obtained to establish a labeled dataset: 312 were used as a training set, 100 as a validation set, and 100 as a testing set. An automatic landmark location system based on the convolutional neural network was developed. This system consisted of a global detection module and a locally modified module. The lateral cephalogram was first fed into the global module to obtain an initial estimate of the landmark's position, which was then adjusted with the locally modified module to improve accuracy. Mean radial error (MRE) and success detection rate (SDR) within the range of 1-4 mm were used to evaluate the method. RESULTS: The MRE of our validation set was 1.127 ± 1.028 mm, and SDR of 1.0, 1.5, 2.0, 2.5, 3.0, and 4.0 mm were respectively 45.95%, 89.19%, 97.30%, 97.30%, and 97.30%. The MRE of our testing set was 1.038 ± 0.893 mm, and SDR of 1.0, 1.5, 2.0, 2.5, 3.0, and 4.0 mm were respectively 54.05%, 91.89%, 97.30%, 100%, 100%, and 100%. CONCLUSIONS: In this study, we proposed a new automatic landmark location system on the basis of the convolutional neural network. The system could detect 37 landmarks with high accuracy. All landmarks are commonly used in clinical practice and could meet the requirements of different cephalometric analysis methods.

[Influencing factors for the quality of bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy in children]. / å„¿ç«¥ç»“è‚ é•œæ£€æŸ¥å‰èšä¹™äºŒé†‡ç”µè§£è´¨æ•£è”åˆé¥®é£ŸæŽ§åˆ¶è‚ é“å‡†å¤‡è´¨é‡çš„å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the influencing factors for the quality of bowel preparation before colonoscopy in children and the association of the interval from the last administration of laxative to the start of colonoscopy (shortly referred to as waiting time) with the quality of bowel preparation. METHODS: A retrospective analysis was performed for the children who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University, from January to November 2020, and received bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy. According to the score of Boston bowel preparation scale, they were divided into two groups: adequate bowel preparation group (n=337) and inadequate bowel preparation group (n=30). Related data were collected from the children in both groups, including general information, possible influencing factors for the quality of bowel preparation, adverse reactions associated with bowel preparation, duration of colonoscopy, and postoperative diagnosis. Univariate and multivariate analyses were used to explore the influencing factors for the quality of bowel preparation. RESULTS: The univariate analysis showed that age, body weight, and waiting time were associated with inadequate bowel preparation (P<0.05). The multivariate analysis showed that older age (OR=2.155, 95%CI: 1.087-4.273, P=0.028) and longer waiting time (OR=1.559, 95% CI: 1.191-2.041, P=0.001) were independent risk factors for inadequate bowel preparation. The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of waiting time was 5.5 hours in determining whether bowel preparation was adequate or not, with a sensitivity of 90.0%, a specificity of 50.7%, and an area under the ROC curve of 0.708. After grouping based on waiting time, it was found that the incidence rate of inadequate bowel preparation in the ≥5.5 hours group was significantly higher than that in the <5.5 hours group [14.0% (27/193) vs 1.7% (3/174), P<0.001]. CONCLUSIONS: For children who use polyethylene glycol electrolyte powder combined with diet control for bowel preparation, older age is an independent risk factor for inadequate bowel preparation before colonoscopy, which may be associated with an insufficient dose of polyethylene glycol in older children. Longer waiting time is also an independent risk factor for inadequate bowel preparation, and it is recommended that the waiting time should not exceed 5.5 hours.

Relationship between periodontitis and microangiopathy in type 2 diabetes mellitus: a meta-analysis.

OBJECTIVE: Whether periodontitis increases the risk of diabetic microangiopathy remains controversial. The present meta-analysis aims to investigate the relationship between periodontitis and diabetic microangiopathy in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, and WanFang data were searched without language restrictions. The methodological quality of the studies included was assessed using Newcastle-Ottawa Scale method, and meta-analysis was performed by Review Manager 5.3. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the risk of periodontitis for diabetic microangiopathy among patients with type 2 diabetes. RESULTS: Thirteen cross-sectional studies, covering 10 570 participants, were included in the present meta-analysis. The results demonstrated that periodontitis was associated with increased risk of type 2 diabetic microangiopathy (OR: 2.43, 95% CI: 1.65-3.56), diabetic retinopathy (OR: 4.33, 95% CI: 2.19-8.55), and diabetic nephropathy (OR: 1.75, 95% CI: 1.07-2.85), while periodontitis was not associated with diabetic neuropathy (OR: 0.99, 95% CI: 0.19-5.12). Subgroup analysis among the studies in Asian (OR: 3.06, 95% CI: 1.94-4.84) and North American (OR: 1.42, 95% CI: 1.08-1.86) populations confirmed the existed association between periodontitis and type 2 diabetic microangiopathy. The relationship still existed in groups with sample size larger than 500 (OR: 1.77, 95% CI: 1.34-2.34) and smaller than 500 (OR: 3.33, 95% CI: 1.38-8.03). A sensitivity analysis confirmed the stability of the results by excluding moderate quality studies or removing articles one after the other. CONCLUSION: Current evidences have proved that periodontitis is associated with increased risk of diabetic microangiopathy in patients with type 2 diabetes mellitus. This conclusion may provide useful evidence for correlated clinical researches. PROSPERO registration number CRD42021247773.

The Preliminary Application of Augmented Reality in Unilateral Orbitozygomatic Maxillary Complex Fractures Treatment.

PURPOSE: Try to apply augmented reality (AR) technique which based on visual recognition artificial marks in the treatment of unilateral Orbitozygomatic Maxillary complex fractures (OZMF), and to explore the feasibility and the application value of the AR for assisting the oral and maxillofacial surgery (OMFS) treatment. METHODS: Based on the AR application JSARToolKit developed on the web, and combining with the self-designed tooth-borne type visual recognition artificial marks to display three-dimensional (3D) image of the region of interest (ROI), virtually designed the position and direction of plate on the jaw and helped OZMF surgery. According to some results to evaluate the postoperative effects, such as imaging, occlusion, facial appearance recovery, patients' satisfaction and operation time. RESULTS: The AR achieved the 3D image of ROI in real time, satisfied information enhancement of real scene, broadened the surgeon's horizons and improved the 3D recognition ability of maxillofacial tissue. After operation, patients had no discomforts, fracture reduction were well healed through imaging examination, and the titanium plate position was consistent with the preoperative planning. What is more, patients' facial appearance and occlusal function recovered well, significantly shorten the intraoperation time. CONCLUSION: Augmented reality technology is an effective method for OZMF treatment but there are still many technical difficulties which need to be get over, and its application in maxillofacial surgery and relevant basic theories are both worth further exploring.

A Phototheranostic Strategy to Continuously Deliver Singlet Oxygen in the Dark and Hypoxic Tumor Microenvironment.

Continuous irradiation during photodynamic therapy (PDT) inevitably induces tumor hypoxia, thereby weakening the PDT effect. In PDT-induced hypoxia, providing singlet oxygen from stored chemical energy may enhance the cell-killing effect and boost the therapeutic effect. Herein, we present a phototheranostic (DPPTPE@PEG-Py NPs) prepared by using a 2-pyridone-based diblock polymer (PEG-Py) to encapsulate a semiconducting, heavy-atom-free pyrrolopyrrolidone-tetraphenylethylene (DPPTPE) with high singlet-oxygen-generation ability both in dichloromethane and water. The PEG-Py can trap the 1 O2 generated from DPPTPE under laser irradiation and form a stable intermediate of endoperoxide, which can then release 1 O2 in the dark, hypoxic tumor microenvironment. Furthermore, fluorescence-imaging-guided phototherapy demonstrates that this phototheranostic could completely inhibit tumor growth with the help of laser irradiation.

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors.

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.

The efficacy of RGD modified liposomes loaded with vinorelbine plus tetrandrine in treating resistant brain glioma.

Brain glioma is one of the most common and devastating intracranial malignancies with a high mortality. Chemotherapy for brain glioma is not ideal due to blood brain barrier (BBB) and multidrug resistance (MDR). The objectives of the present study were to develop a kind of RGD (Arg-Gly-Asp) tripeptide modified vinorelbine plus tetrandrine liposomes to achieve BBB transportation, MDR reversion and glioma cell targeting simultaneously. The studies were performed on glioma cells, resistant glioma cells and glioma-bearing mice. Results showed that the constructed liposomes with suitable physicochemical properties could significantly enhance the transport across BBB, obviously accumulate in glioma cells, and exhibit evident capabilities in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced anticancer efficacy could be attribute to the follows: prolonged elimination half-life (7.093 ± 1.311 h); increased AUC0-24 h (28.92 ± 2.66 mg/L*h); transporting across BBB; enhanced cellular uptake; down-regulation on P-gp (0.49 ± 0.06 fold); inducing apoptosis via activating caspase 8, 9, and 3 (2.40 ± 0.22, 3.57 ± 0.29, and 4.33 ± 0.30 folds, respectively). In conclusion, the RGD modified vinorelbine plus tetrandrine liposomes may offer a promising therapeutic strategy for treatment of brain glioma.

Chemiluminescence of Conjugated-Polymer Nanoparticles by Direct Oxidation with Hypochlorite.

Chemiluminescence (CL) is an advantageous detection tool for in vivo imaging because of the high signal-to-noise ratio of its optical-signal readout, which does not require an external excitation source. Conjugated polymers (CPs) are now used as an energy acceptor in CL nanoparticles to enhance the CL. Here, we demonstrate CL from the direct oxidation of CP backbones in conjugated-polymer nanoparticles (CPNs) by hypochlorite. Such CL CPNs completely avoid the involvement of small-molecule CL donors. The strategy greatly simplifies CL-probes preparation and increases the stability of CL nanoprobes by overcoming the leakage problem of CL donors in nanoparticles. Hypochlorite can oxidize the vinylene bond (C═C) in polyfluorene-vinylene (PFV)/polyphenylenevinylene (PPV) via π2-π2 cycloaddition to form a PFV- or PPV-dioxetane intermediate that is unstable and can spontaneously degrade into PFV- or PPV-aldehyde and generate photons. The dioxetane-intermediate formation was confirmed by UV-vis-absorption, fluorescence, nuclear-magnetic-resonance (1H NMR), and Fourier-transform infrared (FT-IR) spectroscopy. The CL quantum yield (QY) of the brightest CL probe, CPN-poly[(9,9-di(2-ethylhexyl)-9 H-fluorene-2,7-vinylene)- co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (90:10 mol ratio, CPN-PFV- co-MEHPV), was 17.79 einsteins/mol (namely, photons per particle). CPN-PFV- co-MEHPV was size-stable, noncytotoxic, selective, and sensitive for hypochlorite detection. The linear range and the LOD of CPN-PFV- co-MEHPV for ClO- detection are 2-30 and 0.47 µM. Thus, CPN-PFV- co-MEHPV was successfully applied for in vivo imaging of endogenously produced ClO- in living animals. We expect that the represented strategy could be extended to construct other CL nanoprobes for bioimaging and disease diagnosis by simply optimizing and transforming CP backbones; such CL CPNs will have a profound impact on the field of bioimaging.

Application of Digital Diagnosis and Treatment Technique in Benign Mandibular Diseases.

PURPOSE: To explore the feasibility of preoperative planning for treatment of benign mandibular lesions (BML) using digital technologies such as three-dimensional (3D) reconstruction, measurement, visualization as well as image contrast and design of neural positioning protection template (NPPT) in combination with 3D printing technology in the BML diagnosis and treatment. METHODS: The 3D models of BML and inferior alveolar nerves (IAN) of 10 BML patients were reconstructed based on their digital imaging and communications in medicine (DICOM) data using MIMICS16.0 software. The models were used to visualize lesions and nerve contrast measurement and guide design of personalized NPPT and osteotomy after operation modality was determined in order to achieve accurate, minimally invasive operation with shortened intraoperative time. RESULTS: Intraoperative NPPT application could accurately locate lesions and their scope and assist osteotomy. The measurement results were consistent with those of preoperative reconstruction and measurement. The BML were curetted completely without damage IAN. The 10 BML patients had no numbness and other discomforts in the lower lip and mandibular teeth after operation. CONCLUSIONS: The digital diagnosis and treatment technology is an effective method for functional treatment of BML patients and its application could achieve personalized, minimally invasive and precise treatment and save intraoperation time.

Near-Infrared Semiconducting Polymer Brush and pH/GSH-Responsive Polyoxometalate Cluster Hybrid Platform for Enhanced Tumor-Specific Phototheranostics.

Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on the combination of semiconducting polymer brushes and polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation, while the reducing TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the smart pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which has potential for precise tumor-specific phototheranostics with minimal side effects.

Development of a Rapidly Dissolvable Oral Pediatric Formulation for Mefloquine Using Liposomes.

Mefloquine (Mef), a poorly soluble and highly bitter drug, has been used for malaria prophylaxis and treatment. The dosage form for Mef is mostly available as adult tablets, and thus children under the age of 5 suffer from poor medication adherence. We have developed a stable, rapidly dissolvable, and palatable pediatric formulation for Mef using liposomes composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol with a mean diameter of ∼110 nm. Mef was actively loaded into the liposomes via an ammonium sulfate gradient using the solvent-assisted loading technology (SALT) developed in our lab. Complete loading of Mef inside the liposomal core was achieved at a high drug-to-lipid ratio (D/L) of 0.1-0.2 (w/w), and the final drug content in the formulation was ∼8 mg/mL, well above the solubility of Mef (<0.6 mg/mL in simulated fluids). The strong bitterness of Mef was masked by the liposomal encapsulation as measured by an electronic tongue. Incubating the Mef-liposomes (Mef-Lipo) in the simulated gastric fluid (pH 1.2) and the simulated intestinal fluid containing 3 mM sodium taurocholate (pH 6.8) induced changes in liposome size and the polydispersity, resulting in drug release (∼40% in 2 h). However, no drug release from the Mef-Lipo was measured in the bile salt-free intestinal fluid or simulated saliva (0% in 3 h). These data suggest that drug release from the Mef-Lipo was mediated by a low pH and the presence of a surfactant. Pancreatic lipase did not degrade DSPC in the Mef-Lipo after 8 h of incubation nor induce Mef release from the liposomes, indicating that lipid digestion played a minor role for drug release from the Mef-Lipo. In order to improve long-term room temperature storage, the Mef-Lipo was lyophilized to obtain a solid formulation, which was completely dissolvable in water in 10 s and displayed similar in vitro profiles of release as the liquid form. The lyophilized Mef-Lipo was stable at room temperature for >3 months. In mice, orally delivered liquid and lyophilized Mef-Lipo displayed comparable absorption with bioavailability (BA) of 81-86%, while the absorption of the standard Mef suspension was significantly lower with BA of 70% and 20% decreased maximal plasma concentration and area under the curve. Our data suggest that the Mef-Lipo was a stable, palatable, and bioavailable formulation that might be suitable for pediatric use.

A Simple and Improved Active Loading Method to Efficiently Encapsulate Staurosporine into Lipid-Based Nanoparticles for Enhanced Therapy of Multidrug Resistant Cancer.

PURPOSE: This study was aimed at developing a new active loading method to stably encapsulate staurosporine (STS), a water insoluble drug, into lipid-based nanoparticles (LNPs) for drug targeting to tumors. METHODS: A limited amount of DMSO was included during the active loading process to prevent precipitation and facilitate the loading of insoluble STS into the aqueous core of a LNP. The drug loading kinetics under various conditions was studied and the STS-LNPs were characterized by size, drug-to-lipid ratio, drug release kinetics and in vitro potency. The antitumor efficacy of the STS-LNPs was compared with free STS in a mouse model. RESULTS: The drug loading efficiency reached 100% within 15 min of incubation at a drug-to-lipid ratio of 0.31 (mol) via an ammonium gradient. STS formed nano-aggregates inside the aqueous core of the LNPs and was stably retained upon storage and in the presence of serum. A 3-fold higher dose of the STS-LNPs could be tolerated by BALB/c mice compared with free STS, leading to nearly complete growth inhibition of a multidrug resistant breast tumor, while free STS only exhibited moderate activity. CONCLUSION: This simple and efficient drug loading method produced a stable LNP formulation for STS that was effective for cancer treatment.