Utilizing deep learning for automated detection of oral lesions: A multicenter study.

OBJECTIVES: We aim to develop a YOLOX-based convolutional neural network model for the precise detection of multiple oral lesions, including OLP, OLK, and OSCC, in patient photos. MATERIALS AND METHODS: We collected 1419 photos for model development and evaluation, conducting both a comparative analysis to gauge the model's capabilities and a multicenter evaluation to assess its diagnostic aid, where 24 participants from 14 centers across the nation were invited. We further integrated this model into a mobile application for rapid and accurate diagnostics. RESULTS: In the comparative analysis, our model overperformed the senior group (comprising three most experienced experts with more than 10 years of experience) in macro-average recall (85 % vs 77.5 %), precision (87.02 % vs 80.29 %), and specificity (95 % vs 92.5 %). In the multicenter model-assisted diagnosis evaluation, the dental, general, and community hospital groups showed significant improvement when aided by the model, reaching a level comparable to the senior group, with all macro-average metrics closely aligning or even surpassing with those of the latter (recall of 78.67 %, 74.72 %, 83.54 % vs 77.5 %, precision of 80.56 %, 76.42 %, 85.15 % vs 80.29 %, specificity of 92.89 %, 91.57 %, 94.51 % vs 92.5 %). CONCLUSION: Our model exhibited a high proficiency in detection of oral lesions, surpassing the performance of highly experienced specialists. The model can also help specialists and general dentists from dental and community hospitals in diagnosing oral lesions, reaching the level of highly experienced specialists. Moreover, our model's integration into a mobile application facilitated swift and precise diagnostic procedures.

Nicotinamide N-Methyltransferase (NNMT) is Involved in Gastric Adenocarcinoma Immune Infiltration by Driving Amino Acid Metabolism.

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

Correlation Between Serum microRNA-18a Level and Endothelial Function and Prognosis in Female Coronary Heart Disease Patients.

BACKGROUND: The aim was to analyze the correlation between serum microRNA (miR)-18a level, endothelial function, and prognosis in female coronary heart disease (CHD) patients. METHODS: One hundred sixtyfemale patients admitted to our hospital for the first occurrences of chest pain and tightness were divided into CHD and non-CHD groups based on the coronary angiography results. Clinical data, laboratory indexes, serum miR-18a level, and endothelial function [flow-mediated dilation (FMD) function, endothelin 1 (ET-1), and nitric oxide (NO)] were compared. RESULTS: There were no significant differences in clinical data (except CHD family history) between 2 groups. Coronary heart disease group had significantly lower levels of NO and FMD, while significantly higher levels of miR-18a and ET-1 than non-CHD group (P <.05). Pearson correlation showed that serum miR-18a level was positively correlated with ET-1 (r = 0.492, P <.001), and negatively correlated with NO and FMD (r = -0.504, -0.307, P <.001). The receiver operating characteristic) curve showed that the area under the curve of serum miR-18a level in predicting the occurrence of CHD in women was 0.878 (95% CI:  0.828-0.928). Compared with good prognosis group, poor prognosis group had signifi-cantly lower NO, and FMD levels, while higher proportions of acute coronary syndrome, multivessel disease, miR-18a, and ET-1 levels (P <.05). CONCLUSION: The expression of serum miR-18a in female CHD patients was high, which was related to endothelial function. The increase in serum miR-18a level was a risk factor for the occurrence of MACE in female CHD patients during follow-up, and the serum miR-18a level could effectively predict the occurrence of CHD in female patients.

Expanding the clinical phenotype and genetic spectrum of GEMIN5 disorders: Early-infantile developmental and epileptic encephalopathies.

BACKGROUND: Several biallelic truncating and missense variants of the gem nuclear organelle-associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early-infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. PURPOSE: This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub-regional locations. METHODS: We performed whole-exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype-phenotype relationship. RESULTS: Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147-154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603-154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression-bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR-like domain or RBS domain were more likely to be associated with epilepsy. CONCLUSIONS: We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis.

Accuracy of the modified tooth-supported 3D printing surgical guides based on CT, CBCT, and intraoral scanning in maxillofacial region: A comparison study.

BACKGROUND: Tooth-supported surgical guides have demonstrated superior accuracy compared with bone-supported guides. This study aimed to modify the fabrication of tooth-supported guides for compatibility with tumor resection procedures and investigate their accuracy. METHODS: Patients with tumors who underwent osteotomy with the assistance of modified tooth- or bone-supported surgical guides were included. Virtual surgical planning (VSP) was employed to align three dimensional (3D) models extracted from intraoperative computed tomography (CT) images. The distances and angular deviations between the actual osteotomy plane and preoperative plane were recorded. A comparative analysis of osteotomy discrepancies between tooth-supported and bone-supported guides, as well as among tooth-supported guides based on CT, cone-beam CT (CBCT), or intraoral scanner (IOS) was conducted. The factors influencing the precision of the guides were analyzed. RESULTS: Sixty patients with 81 resection planes were included in this study. In the tooth-supported group, the mean deviations in the osteotomy plane and angle were 1.39 mm and 4.30°, respectively, whereas those of the bone-supported group were 2.16 mm and 4.95°. In the tooth-supported isotype guide groups, the mean deviations of the osteotomy plane were 1.39 mm, 1.47 mm, 1.23 mm across CT, CBCT, and IOS, respectively. The accuracy of the modified tooth-supported guides remained consistent regardless of number and position of the teeth supporting the guide and location of the osteotomy lines. CONCLUSIONS: The findings indicate that the modified tooth-supported surgical guides demonstrated high accuracy in the maxillofacial region, contributing to a reduction in the amount of surgically detached soft tissue.

Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ): a multicentre, phase II, single-arm, open-label clinical trial (FRUTINEOGA) protocol.

INTRODUCTION: Curing locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ) with surgery alone is challenging. Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients with locally advanced GC/GEJ, and SOX is the most common neoadjuvant regimen in China. The generally good tolerability in patients and fruquintinib's low potential for drug-drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. A combination of fruquintinib, S-1 and oxaliplatin can be a promising neoadjuvant treatment for locally advanced GC/GEJ. In this phase II study, we aim to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC/GEJ. METHODS AND ANALYSIS: The FRUTINEOGA trial is a prospective, multicentre, phase II, single-arm, open-label clinical trial that will enrol 54 patients. Eligible patients will be registered, enrolled and receive 2-4 cycles of fruquintinib plus SOX, after which surgery will be performed and tumour regression will be evaluated. The primary endpoint is the pathological remission rate, and the secondary endpoints are disease-free survival, overall survival, objective response rate, major pathological response rate and R0 resection rate. ETHICS AND DISSEMINATION: Written informed consent will be required from all patients enrolled, and it will be provided by them. The study protocol received approval from the independent ethical review committee of Guangxi Medical University Cancer Hospital, Wuming Hospital of Guangxi Medical University and Wuzhou Red Cross Hospital, Wuzhou Gongren Hospital (approval number: CS2021(96)). We will submit the finalised paper for publication on completing the analyses. This study will provide valuable insights to clinicians regarding the safety and efficacy of incorporating fruquintinib into SOX as neoadjuvant treatment for locally advanced GC/GEJ. The findings have the potential to inform future research proposals and may guide the use of fruquintinib in the neoadjuvant setting for locally advanced GC/GEJ. TRIAL REGISTRATION NUMBER: NCT05122091.

Sole brachytherapy for inoperable, recurrent, and irradiated salivary gland cancer.

BACKGROUND AND PURPOSE: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs. MATERIALS AND METHODS: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated. RESULTS: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events. CONCLUSIONS: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. METHODS: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. RESULTS: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. CONCLUSIONS: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Case report: splicing effect of a novel heterozygous variant of the NUS1 gene in a child with epilepsy.

NUS1 is responsible for encoding of the Nogo-B receptor (NgBR), which is a subunit of cis-prenyltransferase. Over 25 variants in NUS1 have been reported, and these variants have been found to be associated with various phenotypes, such as congenital disorders of glycosylation (CDG) and developmental and epileptic encephalopathy (DEE). We report on the case of a patient who presented with language and motor retardation, epilepsy, and electroencephalogram abnormalities. Upon conducting whole-exome sequencing, we discovered a novel pathogenic variant (chr6:118024873, NM_138459.5: c.791 + 6T>G) in NUS1, which was shown to cause Exon 4 to be skipped, resulting in a loss of 56 amino acids. Our findings strongly suggest that this novel variant of NUS1 is responsible for the development of neurological disorders, including epilepsy. It is believed that the truncation of Nogo-B receptor results in the loss of cis-prenyltransferase activity, which may be the underlying cause of the disease.

Case report: A novel STXBP1 splice variant and the landscape of splicing-involved STXBP1-related disorders.

STXBP1 variants are one of the most common genetic causes of neurodevelopmental disorders and epilepsy, wherein STXBP1-related disorders are characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of affected patients. However, the spectrums of both genotype and phenotype are quite wide and diverse, with a high baseline variability even for recurrent STXBP1 variants. Until now, no clear genotype-phenotype correlations have been established and multiple disease mechanisms have been proposed for STXBP1-related disorders. Without an ascertained disease cause for many cases of STXBP1 variants, it is challenging to manage this disease in an effective manner and current symptom-based treatments are focused on seizure control only, which has a minimal impact on global development. A novel STXBP1 canonical splice variant, NM_001032221.4:c.578+2T>C, was reported in this study, together with detailed documentation of disease manifestations and treatment management. Further RNA expression analysis revealed abnormal intron retention and possible production of truncated STXBP1 proteins as a likely pathogenic mechanism. More importantly, the landscape of previously understudied STXBP1 splice variants and functional investigations was assessed for the first time to provide a context for the discussion of the complicated genotype-phenotype relationship of STXBP1-related disorders. Future cases of this disorder and a deeper mechanism-based understanding of its pathogenic cause are required for precision medicine and better disease management.

Prediction of the Number of Cumulative Pulses Based on the Photon Statistical Entropy Evaluation in Photon-Counting LiDAR.

Photon-counting LiDAR encounters interference from background noise in remote target detection, and the statistical detection of the accumulation of multiple pulses is necessary to eliminate the uncertainty of responses from the Geiger-mode avalanche photodiode (Gm-APD). The cumulative number of statistical detections is difficult to select due to the lack of effective evaluation of the influence of the background noise. In this work, a statistical detection signal evaluation method based on photon statistical entropy (PSE) is proposed by developing the detection process of the Gm-APD as an information transmission model. A prediction model for estimating the number of cumulative pulses required for high-accuracy ranging with the background noise is then established. The simulation analysis shows that the proposed PSE is more sensitive to the noise compared with the signal-to-noise ratio evaluation, and a minimum PSE exists to ensure all the range detections with background noise are close to the true range with a low and stable range error. The experiments demonstrate that the prediction model provides a reliable estimation of the number of required cumulative pulses in various noise conditions. With the estimated number of cumulative pulses, when the signal photons are less than 0.1 per pulse, the range accuracy of 4.1 cm and 5.3 cm are obtained under the background noise of 7.6 MHz and 5.1 MHz, respectively.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Generation of a X-linked juvenile retinoschisis patient-derived induced pluripotent stem cell line ZOCi004-A.

X-linked juvenile retinoschisis (XLRS), caused by the mutation of RS1 gene, is one of the most common causes of macular degeneration for male adolescents. The mutations and clinical manifestations of the disease are diverse. Neither the relationship between the genotypes and phenotypes, nor the radical treatment like gene therapy has been found by now. Retrospective studies have shown that carbonic anhydrase inhibitors can help reduce cysts. However, the specifically pharmacological mechanism remains unknown. Here, we culture induced pluripotent stem cells by drawing peripheral blood from a patient with XLRS, which are supposed to facilitate related researches.

LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway.

Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Ferroptosis is a new type of peroxidation-driven and iron-dependent cell death. However, the biological functions and exact regulatory mechanisms of ferroptosis in GC remain elusive. Here, we performed RNAi and gene transfection, cell viability assay, lipid peroxidation assay, reactive oxygen species (ROS) assay, glutathione assay, qRT-PCR, Western blotting, and transmission electron microscopy (TEM) to study ferroptosis in gastric cancer. The results revealed that silencing latent transforming growth factor ß binding proteins (LTBP2) can significantly inhibit GC cell proliferation and decrease cellular GSH levels, reduce GPX4 activity, and increase ROS generation and malondialdehyde (MDA) levels, leading to ferroptosis in GC cells. In addition, we demonstrate that suppression of LTBP2 could regulate the p62-Keap1-Nrf2 pathway, thereby downregulating the GPX4 and xCT expression and upregulating the PTGS2 and 4HNE expression. Our findings described a new role of LTBP2 in regulating ferroptosis, which heralds the prospect of ferroptosis-mediated cancer therapy.

Nodal downstaging to ypN0 after neoadjuvant chemotherapy positively impacts on survival of cT4N+ GC/GEJ patients.

BACKGROUND: The prognostic value of histomorphologic regression in primary gastric and gastroesophageal cancers (GC/GEJ) has been previously established, however, the impact of lymph node (LN) regression on survival still remains unclear. METHODS: A prospectively maintained database was reviewed to identify cT4N+ gastric and gastroesophageal cancers (GC/GEJ) after NAC (neoadjuvant chemotherapy). Patients were categorized into two groups based on LN status: cN+/ypN0 (downstaged N0) and cN+/ypN+ (persistent N+), long-term survival were analyzed using Kaplan-Meier survival estimates. RESULTS: In total, 125 patients with cT4N+ GC/GEJ underwent NAC followed by surgery were enrolled. A total of 39 patients (31.2%) had cN+/ypN0 (ypN0) disease, 86 patients (68.8%) had cN+/ypN+ (ypN+) disease. Prognosis in ypN+ patients was significantly worse than those in ypN0 group for 3- and 5-year overall survival (OS) (p < 0.05). The 3-year OS was 83%, 44% in ypN0 and ypN+ group, respectively. The 5-year OS was 75%, 35% in ypN0 and ypN+ group, respectively. Multivariable analysis suggested that multivisceral resection (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.14-0.76, p = 0.009), and ypN+ (HR = 3.42, 95% CI: 1.15-10.13, p =0.027) were independent prognostic factors for OS. CONCLUSION: Nodal downstaging is an important hallmark representing the effectiveness of NAC for GC/GEJ, and it positively impacts on survival of these patients.

Clinical application and accuracy assessment of imaging-based surgical navigation guided 125I interstitial brachytherapy in deep head and neck regions.

Brachytherapy has the advantages of being minimally invasive and highly conformal, and it achieves good results in head and neck tumors. To precisely implant the radioactive seeds according to the preplan in deep head and neck regions, the surgical navigation is applied. This study aims to explore the clinical application and accuracy of imaging-based surgical navigation-guided 125I interstitial brachytherapy in terms of seed position. We included 41 patients with tumors in deep head and neck regions. The brachytherapy treatment plan was designed, and the preplanned data were transferred to the navigation system. Needle implantation and seed delivery were performed under surgical navigation system guidance with or without the combination of individual template. The treatment accuracy was evaluated by comparing seed cluster locations between the preoperative treatment plan and the postoperative treatment outcome. A total of 2879 seeds were delivered. The range, mean and median distances between the geometric centers of the preoperative seed point clusters and the postoperative seed point clusters were 0.8-10.5 mm, 4.5 ± 2.3 mm and 4.1 mm, respectively. The differences between preoperative and postoperative volumes of the minimum bounding box of seed point clusters were nonsignificant. In conclusion, the imaging-based surgical navigation system is a promising clinical tool to provide the preplanned data for interstitial brachytherapy intraoperatively, and it is feasible and accurate for the real-time guidance of needle implantation and seed delivery in deep head and neck regions.

Tumor-targeted biomimetic nanoplatform precisely integrates photodynamic therapy and autophagy inhibition for collaborative treatment of oral cancer.

Oral cancer is a common malignant tumor in the maxillofacial region. Surgical resection is the preferred treatment, but the severe functional impairment after surgery forces us to look for noninvasive treatments. As a promising noninvasive treatment method, photodynamic therapy (PDT) has received widespread attention in the field of cancer therapy, but the inefficient uptake capacity of tumor cells and the damage repair mechanisms limit the actual therapeutic effect. The establishment of a targeted therapy function and autophagy inhibition strategy is considered to be an important way to further enhance the effect of PDT. Based on this, we developed the biomimetic nanomaterial PCN-CQ@CCM. The metal-organic framework material PCN-224 was used as a carrier to load the autophagy inhibitor chloroquine (CQ) and it was coated onto the surface with isolated oral squamous cell carcinoma (OSCC) cell membranes. Owing to the immune evasion and homologous targeting ability of the biomimetic functionalized surface, PCN-CQ@CCM can escape macrophage phagocytosis and homologously adhere to tumor cells, enhancing the retention and uptake of nanomaterials in the tumor microenvironment. After being activated with a 660 nm laser, the generated reactive oxygen species (ROS) triggered the apoptosis pathway, as assessed by mitochondrial damage, and the released CQ further aggravated the ROS lethal pathway by effectively inhibiting the protective autophagic flux. Therefore, PCN-CQ@CCM achieves the precise synergy of PDT and autophagy inhibition through the biomimetic homologous targeting method, and the highly effective tumor suppression effect expands the field of vision for the noninvasive diagnosis and treatment of oral cancer.

A Facile, Protein-Derived Supramolecular Theranostic Strategy for Multimodal-Imaging-Guided Photodynamic and Photothermal Immunotherapy In Vivo.

Theranostic systems that permit both diagnosis and treatment in vivo are highly appealing means by which to meet the demands of precision medicine. However, most such systems remain subject to issues related to complex molecular design and synthesis, potential toxicity, and possible photoactivity changes. Herein, a novel supramolecular theranostic strategy involving biomarker protein activation (BPA) and a host-guest strategy is proposed. To exemplify BPA, a facile "one-for-all" nanotheranostic agent for both albumin detection and cancer treatment is demonstrated, which utilizes a nanoparticulate heavy-atom-free BODIPY dye derivative (B4 NPs). The fluorescence and photoactivity of BODIPY dyes are completely suppressed by aggregation-induced self-quenching in the nanoparticulate state. However, a Balb/c nude mouse model is used to confirm that following the disassembly of injected B4 NPs, BODIPY specifically binds albumin in vivo, accompanied by significantly enhanced biocompatibility and photothermal conversion efficiency. More importantly, this supramolecular host-guest BPA strategy enables the resultant nanoplatform to act as a facile and efficient strategy for photodynamic and photothermal immunotherapy.