Development and application of Chinese medical ontology for diabetes mellitus.

OBJECTIVE: To develop a Chinese Diabetes Mellitus Ontology (CDMO) and explore methods for constructing high-quality Chinese biomedical ontologies. MATERIALS AND METHODS: We used various data sources, including Chinese clinical practice guidelines, expert consensus, literature, and hospital information system database schema, to build the CDMO. We combined top-down and bottom-up strategies and integrated text mining and cross-lingual ontology mapping. The ontology was validated by clinical experts and ontology development tools, and its application was validated through clinical decision support and Chinese natural language medical question answering. RESULTS: The current CDMO consists of 3,752 classes, 182 fine-grained object properties with hierarchical relationships, 108 annotation properties, and over 12,000 mappings to other well-known medical ontologies in English. Based on the CDMO and clinical practice guidelines, we developed 200 rules for diabetes diagnosis, treatment, diet, and medication recommendations using the Semantic Web Rule Language. By injecting ontology knowledge, CDMO enhances the performance of the T5 model on a real-world Chinese medical question answering dataset related to diabetes. CONCLUSION: CDMO has fine-grained semantic relationships and extensive annotation information, providing a foundation for medical artificial intelligence applications in Chinese contexts, including the construction of medical knowledge graphs, clinical decision support systems, and automated medical question answering. Furthermore, the development process incorporated natural language processing and cross-lingual ontology mapping to improve the quality of the ontology and improved development efficiency. This workflow offers a methodological reference for the efficient development of other high-quality Chinese as well as non-English medical ontologies.

Navigation-based endoscopic enucleation (NBEE) of large mandibular cystic lesions involving the ramus.

OBJECTIVE: The aim of this study was to present an innovative surgical protocol, navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the mandibular ramus. METHODS: Twelve patients who presented with a large mandibular cystic lesion involving the mandibular ramus were enrolled in this study. Preoperative planning and intraoperative navigation were performed in all 12 patients. RESULTS: All patients in this study were treated with navigation-based endoscopic enucleation successfully. The follow-up period ranged from 7 to 10 months. Bone regenerated was found in all patients postoperatively. Three patients experienced temporary mandibular nerve palsy, and all relieved within 2 months. No pathological bone fracture was found during surgery. CONCLUSIONS: The use of navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the ramus proved to be an effective method for complete and precise enucleation of the cystic lesion that also preserved the surrounding tissue.

Circularly permuted LOV2 as a modular photoswitch for optogenetic engineering.

Plant-based photosensors, such as the light-oxygen-voltage sensing domain 2 (LOV2) from oat phototropin 1, can be modularly wired into cell signaling networks to remotely control protein activity and physiological processes. However, the applicability of LOV2 is hampered by the limited choice of available caging surfaces and its preference to accommodate the effector domains downstream of the C-terminal Jα helix. Here, we engineered a set of LOV2 circular permutants (cpLOV2) with additional caging capabilities, thereby expanding the repertoire of genetically encoded photoswitches to accelerate the design of optogenetic devices. We demonstrate the use of cpLOV2-based optogenetic tools to reversibly gate ion channels, antagonize CRISPR-Cas9-mediated genome engineering, control protein subcellular localization, reprogram transcriptional outputs, elicit cell suicide and generate photoactivatable chimeric antigen receptor T cells for inducible tumor cell killing. Our approach is widely applicable for engineering other photoreceptors to meet the growing need of optogenetic tools tailored for biomedical and biotechnological applications.

Comparative Genomic Analysis of Cold-Water Coral-Derived Sulfitobacter faviae: Insights into Their Habitat Adaptation and Metabolism.

Sulfitobacter is one of the major sulfite-oxidizing alphaproteobacterial groups and is often associated with marine algae and corals. Their association with the eukaryotic host cell may have important ecological contexts due to their complex lifestyle and metabolism. However, the role of Sulfitobacter in cold-water corals remains largely unexplored. In this study, we explored the metabolism and mobile genetic elements (MGEs) in two closely related Sulfitobacter faviae strains isolated from cold-water black corals at a depth of ~1000 m by comparative genomic analysis. The two strains shared high sequence similarity in chromosomes, including two megaplasmids and two prophages, while both contained several distinct MGEs, including prophages and megaplasmids. Additionally, several toxin-antitoxin systems and other types of antiphage elements were also identified in both strains, potentially helping Sulfitobacter faviae overcome the threat of diverse lytic phages. Furthermore, the two strains shared similar secondary metabolite biosynthetic gene clusters and genes involved in dimethylsulfoniopropionate (DMSP) degradation pathways. Our results provide insight into the adaptive strategy of Sulfitobacter strains to thrive in ecological niches such as cold-water corals at the genomic level.

Various Types of Facial-Angular Artery-Based Flaps for Reconstructing Oral and Maxillofacial Defects Following Cancer Ablation.

BACKGROUND: The flap based on the facial-angular vessels (FAVs) has several names and cannot capture the hemodynamics. AIMS: This study was performed to assess the reliability of various types of flaps based on the FAVs for reconstructing oral and maxillofacial defects following cancer ablation. PATIENTS AND METHODS: Forty-three oral and maxillofacial defects were reconstructed with facial-angular artery island flaps (FAAIF, n =14), including V-Y advancement-type and rotation-type flaps based on FAVs and reverse-flow FAAIFs (R-FAAIF, n =29), including ipsilateral, contralateral rotation, full-thickness, and folded types, based on distal FAVs following cancer ablation. The patients (25 males and 18 females) ranged in age from 18 to 82 years. The lesions included basal cell carcinoma ( n =26), squamous cell carcinoma ( n =8), adenoid cystic carcinoma ( n =3), mucoepidermoid carcinoma ( n =3), verrucous carcinoma ( n =2), and nodular melanoma ( n =1). The tumors were classified as clinical stage I to III in 12, 25, and 6 cases, respectively. Lesions were observed in orbital ( n =4), infraorbital ( n =14), glabellar ( n =2), nasal ( n =4), cheek ( n =10), upper lip ( n =3), palate ( n =4), and lower gingival ( n =2) regions. The defects ranged in size from 2.0×2.5 to 5.0×12.0 cm. The skin paddle ranged in size from 1.5×3.0 to 4.0×12.0 cm. RESULTS: There was 1 flap failure, resulting in a flap success rate of 97.7%. Complications, including hematoma, infection, wound dehiscence, and fistula, occurred in 15 (34.9%) patients. Limitations of mouth opening and ectropion occurred in 12 (28.0%) patients. The esthetic outcomes were satisfactory in 36 (83.7%) patients but were not significantly different between the FAAIF and R-FAAIF groups. The patients were followed up for 6 to 60 months. At the time of the last follow-up, 27 (62.8%) patients were alive with no disease, 9 (20.9%) were alive with disease, and 7 (16.3%) had died due to their disease. There was no significant survival difference between the 2 groups. CONCLUSIONS: Various types of FAV-based flaps are valuable reconstructive options for the treatment of oral and maxillofacial defects following clinical stage I-III cancer ablation.

Maxillectomy and Flap Reconstruction of Maxillary Defects After Cancer Ablation Through the Lip-Split Parasymphyseal Mandibulotomy Approach in Patients With Advanced-Stage Maxillary Malignant Tumors.

BACKGROUND: The conventional approach for maxillectomy has some common and serious complications. AIMS: The present study evaluated the outcomes of maxillectomy and flap reconstruction after cancer ablation using the lip-split parasymphyseal mandibulotomy (LPM) approach. METHODS: Twenty-eight patients with malignant tumors, including squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma, underwent maxillectomy through the LPM approach. Brown classes II and III were reconstructed with the facial-submental artery submental island flap, an extensive segmental pectoralis major myocutaneous flap, and a free anterolateral thigh flap with the use of a titanium mesh, respectively. RESULTS: All proximal margin frozen section specimens showed negative surgical margins. Anterolateral thigh flap failure occurred in 1 patient, whereas ophthalmic and mandibulotomy complications developed in 4 and 7 patients, respectively. In all, 84.6% of the patients had satisfactory or excellent lip esthetic results. Of the patients, 57.1% were alive with no evidence of disease, whereas 28.6% were alive with disease and 14.3% died of local recurrence or distant metastasis. No significant survival difference was evident among the squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma groups. CONCLUSIONS: The LPM approach can provide good surgical access, facilitating maxillectomy in advanced-stage malignant tumors with minimal morbidity. Facial-submental artery submental island flap and anterolateral thigh flap or extensive segmental pectoralis major myocutaneous flap with a titanium mesh are ideal techniques for reconstructing Brown classes II and III defects, respectively.

CD79A work as a potential target for the prognosis of patients with OSCC: analysis of immune cell infiltration in oral squamous cell carcinoma based on the CIBERSORTx deconvolution algorithm.

OBJECTIVE: To analyze the abundance of infiltrating tumor immune cells in patients with oral squamous cell carcinoma (OSCC) and to search for potential targets that can predict patient prognosis. METHODS: A total of 400 samples from 210 patients with OSCC were collected using The Cancer Genome Atlas (TCGA) database. CIBERSORTx was used to evaluate the infiltration abundance of tumor immune cells. Potential target genes were searched to predict patient prognosis through case grouping, differential analysis, and enrichment analysis. Surgical excisional tissue sections of patients with oral squamous cell carcinoma admitted to the Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Shantou University Medical College, from 2015 to 2018 were collected and followed up. RESULTS: The CIBERSORTx deconvolution algorithm was used to analyze the infiltration abundance of immune cells in the samples. Cases with a high infiltration abundance of naive and memory B lymphocytes improved the prognosis of OSCC patients. The prognosis of patients with low CD79A expression was significantly better than that of patients with high CD79A expression. CONCLUSION: CD79A can predict the infiltration abundance of B lymphocytes in the tumor microenvironment of patients with OSCC. CD79A is a potential target for predicting the prognosis of patients with OSCC. This study provides novel ideas for the treatment of OSCC and for predicting patient prognosis.

Application of an L-shaped anterolateral thigh flap in reconstruction after hemiglossectomy.

OBJECTIVE: Tongue defect reconstruction is one of the key components of tongue cancer surgery. In this study, we used an L-shaped flap design adopted as a simple and efficient method to repair tongue defects after hemiglossectomy. Furthermore, we evaluated and contrasted the clinical effects of two methods, the L-shaped and traditional methods. STUDY DESIGN: Fifteen patients in the L-shaped group and 20 patients in the traditional group were evaluated and compared in terms of postoperative complications, dysphagia, language function and appearance satisfaction. RESULTS: The results (Table 1) showed that there were 2 cases of donor area invalid traumas, and 2 patients had scar hyperplasia in the traditional group. The degree of global and functional dysphagia of the L-shaped group (2.60 ± 0.29 and 11.47 ± 1.38) was lower than that of the traditional group (3.55 ± 0.29 and 15.75 ± 1.22) (P < 0.05). In the language evaluation, the traditional group (3.20 ± 0.26) had lower scores than the L-shaped group (4.13 ± 0.30) (P < 0.05). CONCLUSION: The L-shaped ALTP flap is a simple and efficient modification of ALTP, that can be used for half-tongue repair after radical operations for tongue cancer. It has better performance in the recovery of dysphagia and language function than the traditional ALTP flap.

Progression and postoperative complications of osteoradionecrosis of the jaw: a 20-year retrospective study of 124 non-nasopharyngeal cancer cases and meta-analysis.

BACKGROUND: To assess the contributing risk factors for the progression of, and the postoperative poor prognosis associated with, osteoradionecrosis of jaw (ORNJ) following non-nasopharyngeal cancer treatment in head and neck. METHODS: A retrospective study of 124 non-nasopharyngeal carcinoma patients in head and neck treated at one institution between 2001 and 2020 was conducted. A cumulative meta-analysis was conducted according to PRISMA protocol and the electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. After assessing surgery with jaw lesions as a risk factor for the occurrence of ORNJ, 124 cases were categorized into two groups according to the "BS" classification, after which jaw lesions, chemotherapy, flap reconstruction and onset time of ORNJ were analyzed through the chi-square test and t-test to demonstrate the potential association between them and the progression of ORNJ. Postoperative outcomes of wound healing, occlusal disorders, and nerve injury were statistically analyzed. RESULTS: With the statistically significant results of the meta-analysis (odds ratio = 3.07, 95% CI: 1.84-5.13, p < 0.0001), the chi-square test and t-test were used to validate our hypotheses and identified that surgery with jaw lesions could aggravate the progression and accelerate the appearance of ORNJ. Patients who underwent chemotherapy tended to suffer from severe-to-advanced osteonecrosis but did not shorten the onset time of ORNJ. Flap reconstruction presented obvious advantages in wound healing (p < 0.001) and disordered occlusion (p < 0.005). The mean onset time of ORNJ in non-nasopharyngeal cancer patients (4.5 years) was less than that in patients with nasopharyngeal cancer (NPC) (6.8 years). CONCLUSIONS: Iatrogenic jaw lesions are evaluated as a significant risk factor in the occurrence and progression of ORNJ in non-nasopharyngeal carcinoma patients who tend to have more severe and earlier osteonecrosis after radiotherapy than NPC patients. Flap reconstruction is a better choice for protecting the remaining bone tissue and reducing postoperative complications of ORNJ.

Upregulation of long non-coding RNA FOXD2-AS1 promotes progression and predicts poor prognosis in tongue squamous cell carcinoma.

BACKGROUND: Accumulating evidences suggest that lncRNA FOXD2-AS1 plays an important role in tumor progression, however, its function in tongue squamous cell carcinoma (TSCC) remains unknown. This research aims to investigate the function and mechanism of FOXD2-AS1 in the modulation of tongue squamous cell carcinoma progression. METHODS: Expression of FOXD2-AS1 was detected in TSCC tissues and TCGA data. Receiver operating characteristic curves (ROCs) analysis and bioinformatic analysis of TCGA data were performed to investigate the role of FOXD2-AS1 in TSCC prognosis. After siRNA-mediated downregulation of FOXD2-AS1, wound healing assay, Transwell migration and invasion assays, and MTS proliferation assay were conducted to explore the effects that FOXD2-AS1 exerted on SCC-9 and CAL-27 cell lines. Western blotting was performed to detect the downstream protein changes. RESULTS: Compared to the normal tissues and samples, FOXD2-AS1 significantly highly expressed in TSCC tissues and in TSCC samples of TCGA data, and high expression of FOXD2-AS1 was associated with lymphatic metastasis and poor TNM stages. ROC analysis and bioinformatic analysis of TCGA data further suggested that high expression of FOXD2-AS1 was associated with TSCC poor prognosis. Downregulation of FOXD2-AS1 inhibited the migration and invasion of SCC-9 and CAL-27 cell lines. Western blotting showed that the expression of p-p44 and p-p65 downregulated after FOXD2-AS1 knockdown. CONCLUSION: High expression of FOXD2-AS1 promotes TSCC progression through modulating NF-kB and ERK MAPK signaling pathways and is associated with TSCC poor prognosis, it could be a novel therapeutic target and prognostic biomarker for TSCC.

The Mammalian Target of Rapamycin-70-kDa Ribosomal Protein S6 Kinase Axis Inhibits the Biological Function of Tongue Squamous Cell Carcinoma.

PURPOSE: Studies have shown the mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 kinase (p70S6K) to be tumor suppressors in many cancers. These factors may have synergistic functions in tongue squamous cell carcinoma (TSCC), which is the most common malignant cancer in the oral region. We aimed to investigate the expression of the mTOR-p70S6K axis in TSCC patients and its biological function in TSCC cell lines. MATERIALS AND METHODS: Sixty-eight TSCC patients were included in this study, and their features, including age, gender, tumor differentiation, lymphatic metastasis, and clinical stage, were recorded. The expression of mTOR and p70S6K was detected by immunohistochemistry. Small interfering RNA constructs were delivered into TSCC cells to downregulate mTOR and p70S6K expression in vitro. After transfection, cell proliferation, migration or invasion, apoptosis, and chemoresistance assays were performed to examine cellular variations of biological function. RESULTS: High expression of the mTOR-p70S6K axis was associated with higher tumor stage, lymph node metastasis, and poor tumor differentiation. Suppression of mTOR and p70S6K in TSCC cells resulted in the inhibition of cell proliferation, metastases, and chemoresistance. Inhibiting mTOR expression could inhibit p70S6K expression but not vice versa. CONCLUSIONS: The high expression of mTOR and p70S6K is closely associated with malignant characterization of TSCC patients, and it could inhibit biological functions of TSCC cell lines. Taken together, the mTOR-p70S6K axis may serve as a potential therapeutic strategy for TSCC.

Prevalence and Genetic Analysis of mcr-3-Positive Aeromonas Species from Humans, Retail Meat, and Environmental Water Samples.

The mobile colistin resistance gene mcr-3 is globally disseminated in both Enterobacteriaceae and Aeromonas species, with the latter potentially serving as a reservoir for this gene. Here, we investigated the prevalence of mcr-3 in rectal swabs from humans, in food-producing animals and their products, and in the aquatic environment, and we investigated the genetic relationships between the mcr-3-positive isolates. An enriched broth screening method was used to detect mcr-3 in samples, and species identification of isolates from positive samples was carried out by matrix-assisted laser desorption ionization-time of flight mass spectrometry and shotgun sequencing. All mcr-3-positive isolates were subjected to antimicrobial susceptibility testing, conjugation, and whole-genome sequencing. Ten Aeromonas isolates, including 2 from human rectal swabs, 1 from pork, 3 from chicken meat, and 4 from the aquatic environment, were positive for mcr-3, but only 2 showed resistance to colistin. In addition to the mcr-3 variants identified previously (the novel variants were termed mcr-3.13 to mcr-3.18), all isolates harbored mcr-3-like genes downstream of the mcr-3 variants. The MCR-3.13 to MCR-3.18 proteins exhibited only 89.2% to 96.1% amino acid identity to the original MCR-3 protein. Whole-genome sequence analysis indicated diversity within the genetic environments of mcr-3-positive Aeromonas isolates and possible transmission between different sources in China and even worldwide. Close relationships between mcr-3-positive and mcr-3-negative Aeromonas isolates suggested that mcr-3 might be common in Aeromonas species, which are not inherent hosts of mcr-3 but may act as an important reservoir of this mobile colistin resistance gene.

Removal of the Residual Roots Displaced Into the Maxillary Sinus via Endoscopy.

Minimally invasive endoscopic surgery has been developed for various indications in the craniomaxillofacial area. The case report presented in this article is focused on the possibility of removing the residual roots displaced into the maxillary sinus by means of an endoscopic technique. When planning endoscopic surgery to access the residual roots displaced in the maxillary sinus, we performed 2 different approaches into the maxillary sinus, a transnasal approach through the middle or inferior turbinate and transoral approach via the anterior maxillary sinus wall. The endoscopic surgical approach described is reliable and minimally invasive for removing the residual roots displaced into the maxillary sinus. Therefore, we concluded that the application of this clinical procedure is worth promoting.

Occurrence of Plasmid- and Chromosome-Carried mcr-1 in Waterborne Enterobacteriaceae in China.

The aim of this study was to investigate the prevalence of the polymyxin resistance gene mcr-1 in Enterobacteriaceae from environmental water sources in Hangzhou, China. Colistin-resistant bacteria were isolated from environmental water samples using an enrichment broth culture method, were screened for mcr-1, and then were analyzed for the location and transferability of mcr-1 Isolates positive for mcr-1 were further examined to determine their susceptibility profiles and were screened for the presence of additional resistance genes. Twenty-three mcr-1-positive isolates (16 Escherichia coli, two Citrobacter freundii, two Klebsiella oxytoca, two Citrobacter braakii, and one Enterobacter cloacae) were isolated from 7/9 sampling locations; of those, eight mcr-1-positive isolates also contained ß-lactamase-resistance genes, eight contained qnrS, and 10 contained oqx No mcr-2-positive isolates were identified. The majority of isolates demonstrated a low to moderate level of colistin resistance. Transconjugation was successfully conducted from 14 of the 23 mcr-1-positive isolates, and mcr-1 was identified on plasmids ranging from 60 to 220 kb in these isolates. Conjugation and hybridization experiments revealed that mcr-1 was chromosome-borne in only three isolates. Pulsed-field gel electrophoresis showed that the majority of E. coli isolates belonged to different clonal lineages. Multilocus sequence typing analysis revealed that sequence type 10 (ST10) was the most prevalent, followed by ST181 and ST206. This study demonstrates the utility of enrichment broth culture for identifying environmental mcr-1-positive isolates. Furthermore, it highlights the importance of responsible agriculture and clinical use of polymyxins to prevent further widespread dissemination of polymyxin-resistant pathogens.

Downregulation of nucleophosmin expression inhibited proliferation and induced apoptosis in salivary gland adenoid cystic carcinoma.

BACKGROUND: This study aimed to explore the relationship between nucleophosmin (NPM1) and patient clinical characteristics. Moreover, we investigated the effect of NPM1 in tumor proliferation and apoptosis of salivary gland adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: NPM1 expression was examined in 74 specimens of SACC and 31 non-cancerous epithelium adjacent to carcinoma (NCEAC) by immunohistochemistry (IHC). RNA interference technology was used to silence NPM1 expression in SACC cells. We used transwell culture assay, cell counting kit-8 tests, and colony formation assay to test the proliferation, cisplatin resistance, migration, and invasiveness of SACC cells. RESULTS: The nuclear and cytoplasmic expression of NPM1 in SACC tissue was overexpressed and was tightly linked to perineural invasion and lymph node metastasis. The downregulation of NPM1 inhibited proliferation and induced apoptosis in SACC cells. Knockdown of NPM1 expression had no effect on chemoresistance migration, or invasiveness. CONCLUSIONS: NPM1 may play an important role in tumor progress in SACC and is a potential biomarker for SACC.

Application of Computer-Assisted Design and Manufacturing-Fabricated Artificial Bone in the Reconstruction of Craniofacial Bone Defects.

PURPOSE: The purpose of this study was to evaluate the clinical application of individual craniofacial bone fabrications using computer-assisted design (CAD)-computer-assisted manufacturing technology for the reconstruction of craniofacial bone defects. MATERIALS AND METHODS: A total of 8 patients diagnosed with craniofacial bone defects were enrolled in this study between May 2007 and August 2010. After computed tomography scans were obtained, the patients were fitted with artificial bone that was created using CAD software, rapid prototyping technology, and epoxy-methyl acrylate resin and hydroxyapatite materials. The fabrication was fixed to the defect area with titanium screws, and soft tissue defects were repaired if necessary. RESULTS: The fabrications were precisely fixed to the defect areas, and all wounds healed well without any serious complications except for 1 case with intraoral incision dehiscence, which required further treatment. Postoperative curative effects were retrospectively observed after 6 to 48 months, acceptable anatomic and cosmetic outcomes were obtained, and no rejections or other complications occurred. CONCLUSIONS: The use of CAD-computer-assisted manufacturing technology-assisted epoxy-methyl acrylate resin and hydroxyapatite composite artificial bone to treat patients with craniofacial bone defects could enable the precise reconstruction of these defects and obtain good anatomic and cosmetic outcomes.

Detecting recurrent disease and surgical outcomes in patients with locally advanced tongue cancer after multimodal treatment using ¹8F-FDG-PET/CT.

The purpose of this study was to evaluate the utility of ¹8F-fluorodeoxyglucose positron emission tomography/computed tomography (FPCT) parameters for detecting recurrent disease and the outcomes of salvage surgery in patients with locally advanced oral tongue squamous cell carcinoma (TSCC) after multimodal treatment. In total, 69 patients with locally advanced TSCC were treated with multimodal therapy. All patients underwent whole-body FPCT scans 4-10 months after the initial surgery. The analysis included FPCT parameters, such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Histological examination was used as the reference standard. Patients with recurrent TSCC underwent salvage surgery or surgery plus systemic treatment. This study included 69 patients: 36 in the recurrent TSCC group and 33 in the non-recurrent TSCC group. The SUVmax, MTV, and TLG in the recurrent TSCC group were 11.3 ± 3.6, 28.3 ± 15.6 cm3, and 113.2 ± 46.8 g, respectively; these values were 5.9 ± 3.6, 5.1 ± 2.2 cm3, and 13.4 ± 4.8 g, in the non-recurrent TSCC group respectively. The two groups had significant differences in terms of SUVmax, MTV, and TLG. In the recurrent TSCC group, 91.6 % of patients presented with local, locoregional, and regional disease and underwent salvage surgery plus systemic therapy, whereas 8.4 % had locoregional recurrence with distant metastases alone and underwent surgery plus systemic therapy. The patients were followed up for 12-60 months; 19 and 20 patients in the recurrent and non-recurrent TSCC groups showed no evidence of disease, whereas 11 and 8 were alive with the disease. Local recurrence or distant metastases led to the deaths of six patients in the recurrent TSCC group and five in the non-recurrent TSCC group. No significant differences in survival were observed between the two groups. FPCT parameters can detect the recurrence of locally advanced TSCC after multimodal treatment. Early salvage surgery can improve the treatment outcomes for recurrent TSCC.

Erratum: EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.59331.].

Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling.

BACKGROUND: EGFR is an important signal involved in tumor growth that can induce tumor metastasis and drug resistance. Exploring targets for effective EGFR regulation is an important topic in current research and drug development. Inhibiting EGFR can effectively inhibit the progression and lymph node metastasis of oral squamous cell carcinoma (OSCC) because OSCC is a type of cancer with high EGFR expression. However, the problem of EGFR drug resistance is particularly prominent, and identifying a new target for EGFR regulation could reveal an effective strategy. METHODS: We sequenced wild type or EGFR-resistant OSCC cells and samples from OSCC patients with or without lymph node metastasis to find new targets for EGFR regulation to effectively replace the strategy of directly inhibiting EGFR and exert an antitumor effect. We then investigated the effect of LCN2 on OSCC biological abilities in vitro and in vivo through protein expression regulation. Subsequently, we elucidated the regulatory mechanism of LCN2 through mass spectrometry, protein interaction, immunoblotting, and immunofluorescence analyses. As a proof of concept, a reduction-responsive nanoparticle (NP) platform was engineered for effective LCN2 siRNA (siLCN2) delivery, and a tongue orthotopic xenograft model as well as an EGFR-positive patient-derived xenograft (PDX) model were applied to investigate the curative effect of siLCN2. RESULTS: We identified lipocalin-2 (LCN2), which is upregulated in OSCC metastasis and EGFR resistance. Inhibition of LCN2 expression can effectively inhibit the proliferation and metastasis of OSCC in vitro and in vivo by inhibiting EGFR phosphorylation and downstream signal activation. Mechanistically, LCN2 binds EGFR and enhances the recycling of EGFR, thereby activating the EGFR-MEK-ERK cascade. Inhibition of LCN2 effectively inhibited the activation of EGFR. We translated this finding by systemic delivery of siLCN2 by NPs, which effectively downregulated LCN2 in the tumor tissues, thereby leading to a significant inhibition of the growth and metastasis of xenografts. CONCLUSIONS: This research indicated that targeting LCN2 could be a promising strategy for the treatment of OSCC.