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Extracellular vesicles (EVs) are emerging as promising carriers for the delivery of therapeutic biologics. Genetic engineering represents a robust strategy for loading proteins of interest into EVs. Identification of EV-enriched proteins facilitates protein cargo loading efficiency. Many EV-enriched proteins are sorted into EVs via an endosomal sorting complex required for transport (ESCRT)-dependent pathway. In parallel, viruses hijack this EV biosynthesis machinery via conserved late domain motifs to promote egress from host cells. Inspired by the similarity of biogenesis between EVs and viruses, we developed a synthetic, Late domain-based EV scaffold protein that enables the display of a set of single chain variable fragments (scFvs) on the EV surface. We named this scaffold the Late domain-based exosomal antibody surface display platform (LEAP). We applied the LEAP scaffold to reprogramme HEK293T cell-derived EVs to elicit T-cell anti-tumor immunity by simultaneously displaying αPD-L1 and αCD3 scFvs on the EV surface (denoted as αPD-L1×αCD3 bispecific T-cell engaging exosomes, BiTExos). We demonstrated that αPD-L1×αCD3 BiTExos actively redirected T cells to bind to PD-L1+ tumor cells, promoting T-cell activation, proliferation and tumoricidal cytokine production. Furthermore, the αPD-L1×αCD3 BiTExos promoted T-cell infiltration into the tumor microenvironment to mitigate the tumor burden in vivo. Our study suggested that the LEAP scaffold may serve as a platform for EV surface display and could be applied for a broad range of EV-based biomedical applications.
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Antígeno B7-H1 , Complexo CD3 , Vesículas Extracelulares , Anticorpos de Cadeia Única , Linfócitos T , Humanos , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Animais , Complexo CD3/imunologia , Complexo CD3/metabolismo , Células HEK293 , Linfócitos T/imunologia , Linfócitos T/metabolismo , Camundongos , Anticorpos de Cadeia Única/imunologia , Exossomos/metabolismo , Exossomos/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Ativação Linfocitária/imunologiaRESUMO
Based on the disaster-pregnant environment and development characteristics of landslide disasters in the western region of Henan Province, a generalized model was established by taking the "oblique-cut" locking rock slope in the layered rock slope as the research object. The numerical simulation method was used to analyze the deformation and failure mechanism and stability influence law of the oblique-cut locking rock slope in western Henan under rainfall conditions. The results show that the inclination angle of the weak interlayer directly affects the deformation and failure characteristics of the slope rock mass. With the increase of the geometric parameters of the slope and the inclination angle of the weak interlayer, the failure mechanism is manifested as the slip shear failure along the level at the foot of the slope â the slip shear failure along the level at the foot of the slope (the sliding surface moves upward) â the shear failure in the middle of the slope surface â the slip shear failure along the level at the foot of the slope (the sliding surface moves downward) â the uplift shear failure at the lower edge of the rock layer. When the dip angle of the weak interlayer is constant, the slope stability decreases gradually with the increase in slope gradient and slope height, and the geometric factors of the slope control the overall change trend of the slope stability coefficient. When the slope is greater than 55° and the slope height is greater than 55 m, the shear stress of the slope locking section exceeds its shear strength, and the probability of landslide instability is greatly increased.
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The silicon nitride (Si3N4) coating exhibits promising potential in oral applications due to its excellent osteogenic and antibacterial properties. However, a comprehensive investigation of Si3N4 coatings in the context of dental implants is still lacking, especially regarding their corrosion resistance and in vivo performance. In this study, Si3N4 coatings were prepared on a titanium surface using the nonequilibrium magnetron sputtering method. A systematic comparison among the titanium group (Ti), Si3N4 coating group (Si3N4-Ti), and sandblasted and acid-etched-treated titanium group (SLA-Ti) has been conducted in vitro and in vivo. The results showed that the Si3N4-Ti group had the best corrosion resistance and antibacterial properties, which were mainly attributed to the dense structure and chemical activity of Si-O and Si-N bonds on the surface. Furthermore, the Si3N4-Ti group exhibited superior cellular responses in vitro and new bone regeneration and osseointegration in vivo, respectively. In this sense, silicon nitride coating shows promising prospects in the field of dental implantology.
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Antibacterianos , Materiais Revestidos Biocompatíveis , Implantes Dentários , Osteogênese , Compostos de Silício , Titânio , Titânio/química , Titânio/farmacologia , Compostos de Silício/química , Compostos de Silício/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Osteogênese/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Animais , Propriedades de Superfície , Osseointegração/efeitos dos fármacos , Camundongos , Teste de Materiais , CorrosãoRESUMO
OBJECTIVE: Patients undergoing oral and maxillofacial flap reconstruction often need blood transfusions due to massive blood loss. With the increasing limitations of allogeneic blood transfusion (ABT), doctors are considering acute normovolemic hemodilution (ANH) because of its advantages. By comparing the differences in the (Δ) blood indices and postoperative complications of patients receiving ABT or ANH during the reconstruction and repair of oral and maxillofacial tumor flaps, this study's purpose was to provide a reference for the clinical application of ANH. METHODS: The clinical data of 276 patients who underwent oral and maxillofacial flap reconstruction from September 25, 2017, to October 11, 2021, in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, were retrospectively analyzed. According to the intraoperative blood transfusion mode, the patients were divided into two groups: ABT and ANH. The differences in the (Δ) blood indices and the incidence of postoperative complications between the groups were analyzed. RESULTS: Among the 276 patients who had ANH (124/276) and ABT (152/276), there were no differences in (Δ) Hb, (Δ) PT, or (Δ) FIB (P > 0.05), while (Δ) WBC, (Δ) PLT, (Δ) APTT and (Δ) D-dimer were significantly different (P < 0.05). The blood transfusion method was not an independent factor for flap crisis (P > 0.05). The wound infection probability in patients with high post-PTs was 1.953 times greater than that in patients with low post-PTs (OR = 1.953, 95% CI: 1.232 â¼ 3.095, P = 0.004). A normal or overweight BMI was a protective factor for pulmonary infection, and the incidence of pulmonary infection in these patients was only 0.089 times that of patients with a low BMI (OR = 0.089, 95% CI: 0.017 â¼ 0.462). Moreover, a high ASA grade promoted the occurrence of pulmonary infection (OR = 6.373, 95% CI: 1.681 â¼ 24.163). The blood transfusion mode (B = 0.310, ß = 0.360, P < 0.001; ANH: ln hospital stay = 2.20 ± 0.37; ABT: ln hospital stay = 2.54 ± 0.42) improved the length of hospital stay. CONCLUSION: Preoperative and postoperative blood transfusion (Δ) Hb, (Δ) PT, and (Δ) FIB did not differ; (Δ) WBC, (Δ) PLT, (Δ) APTT, and (Δ) D-dimer did differ. There was no difference in the effects of the two blood transfusion methods on flap crisis, incision infection or lung infection after flap reconstruction, but ANH resulted in a 3.65 day shorter average hospital stay than did ABT.
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Transfusão de Sangue , Hemodiluição , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Retalhos Cirúrgicos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , Hemodiluição/métodos , Adulto , Idoso , Procedimentos Cirúrgicos Bucais/efeitos adversos , Procedimentos Cirúrgicos Bucais/métodos , Perda Sanguínea CirúrgicaRESUMO
Identity recognition as the first barrier of intelligent security plays a vital role, which is facing new challenges that are unable to meet the need of intelligent era due to low accuracy, complex configuration and dependence on power supply. Here, a finger temperature-driven intelligent identity recognition strategy is presented based on a thermogalvanic hydrogel (TGH) by actively discerning biometric characteristics of fingers. The TGH is a dual network PVA/Agar hydrogel in an H2O/glycerol binary solvent with [Fe(CN)6]3-/4- as a redox couple. Using a concave-arranged TGH array, the characteristics of users can be distinguished adequately even under an open environment by extracting self-existent intrinsic temperature features from five typical sites of fingers. Combined with machine learning, the TGH array can recognize different users with a high average accuracy of 97.6%. This self-powered identity recognition strategy is further applied to a smart lock, attaining a more reliable security protection from biometric characteristics than bare passwords. This work provides a promising solution for achieving better identity recognition, which has great advantages in intelligent security and human-machine interaction toward future Internet of everything.
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The objective of this study is to verify the role of digital modified parotid tumor zoning method in modified parotid incision. The data of patients with parotid benign tumors from November 2021 to December 2023 were collected. Through the use of digital technology for soft tissue reconstruction, the parotid tumor was divided into four areas according to the digital image marker points. We designed the surgical incision according to the parotid gland division, found that it was feasible to guide the incision selection by division, and summarized the common incision and division corresponding, zone I was I and V-shaped incision, zone II was V incision, zone III was V and C- shaped incision, and zone IV was C- shaped incision. We conclude that the digital modified parotid gland zoning method can provide a better distinction in the surgical incision, and provide a better cosmetic incision and prognosis.
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OBJECTIVE: This study aims to use machine learning techniques together with radiomics methods to build a preoperative predictive diagnostic model from spiral computed tomography (CT) images. The model is intended for the differential diagnosis of common jaw cystic lesions. STUDY DESIGN: Retrospective, case-control study. SETTING: This retrospective study was conducted at Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Guangzhou, Guangdong, China). All the data used to build the predictive diagnostic model were collected from 160 patients, who were treated at the Department of Oral and Maxillofacial Surgery at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between 2019 and 2023. METHODS: We included a total of 160 patients in this study. We extracted 107 radiomic features from each patient's CT scan images. After a feature selection process, we chose 15 of these radiomic features to construct the predictive diagnostic model. RESULTS: Among the preoperative predictive diagnostic models built using 3 different machine learning methods (support vector machine, random forest [RF], and multivariate logistic regression), the RF model showed the best predictive performance. It demonstrated a sensitivity of 0.923, a specificity of 0.643, an accuracy of 0.825, and an area under the receiver operating characteristic curve of 0.810. CONCLUSION: The preoperative predictive model, based on spiral CT radiomics and machine learning algorithms, shows promising differential diagnostic capabilities. For common jaw cystic lesions, this predictive model has potential clinical application value, providing a scientific reference for treatment decisions.
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Aprendizado de Máquina , Humanos , Estudos Retrospectivos , Feminino , Masculino , Diagnóstico Diferencial , Estudos de Casos e Controles , Adulto , Pessoa de Meia-Idade , Cistos Maxilomandibulares/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Valor Preditivo dos Testes , Idoso , RadiômicaRESUMO
The differences in geomechanical properties and the uncertainty in the spatial distribution of Bimrock pose significant challenges to the construction and disaster prediction of geotechnical engineering. To clarify the geomechanical characteristics of Bimrock, this paper summarizes the basic concepts and classification methods of Bimrock at home and abroad. It discusses the methods and characteristics of determining the geometric features of Bimrock blocks and explores the influencing factors and laws of failure modes and strength under different stress states of Bimrock. The study finds that the failure mode of Bimrock is mainly influenced by factors such as block proportion, degree of welding between blocks and matrix, strength ratio between blocks and matrix, and geometric properties of blocks. Among these factors, block proportion is the most significant, and the degree of welding is a controlling factor. However, due to the complexity of Bimrock structures, there is a lack of applicable methods and mechanical models for the evaluation of geomechanical characteristics of Bimrock in engineering practice. This article also explores the influence and research methods of the geological characteristics of Bimrock in slope and tunnel engineering and, finally, provides prospects for the future research trends relating to Bimrock.
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A new heat source combination, consisting of a uniform body heat source and a tilted double ellipsoidal heat source, has been developed for cold metal transfer (CMT) wire-arc additive manufacturing of Mg-Gd-Y-Zn-Zr alloy. Simulations were conducted to analyze the temperature field and stress distribution during the process. The optimal combination of feeding speed and welding speed was found to be 8 m/min and 8 mm/s, respectively, resulting in the lowest thermal accumulation and residual stress. Z-axis residual stress was identified as the main component of residual stress. Electron Backscatter Diffraction (EBSD) testing showed weak texture strength, and Kernel Average Misorientation (KAM) analysis revealed that the 1st layer had the highest residual stress, while the 11th layer had higher residual stress than the 6th layer. Microhardness in the 1st, 11th, and 6th layers varies due to residual stress impacts on dislocation density. Higher residual stress increases dislocation density, raising microhardness in components. The experimental results were highly consistent with the simulated results.
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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.
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Endoscopia , Mandíbula , Humanos , Mandíbula/cirurgia , Endoscopia/métodos , Osteotomia/métodosRESUMO
A facile Z-scheme AgCl/BiOCl heterojunction photocatalyst with oxygen vacancies was fabricated by a water-bath method. The structural, morphological, optical and electronic properties of as-synthesized samples were systematically characterized. The oxygen vacancies were confirmed by EPR, which could optimize the band-gap of the AgCl/BiOCl heterojunction and improve the photo-induced electron transfer. The optimized AgCl/BiOCl heterojunction showed excellent photocatalytic degradation efficiency (82%) for tetracycline (TC). Simultaneously, E. coli was completely inactivated within 60 min due to the AgCl/BiOCl heterojunction. The elevated catalytic activity of the optimal AgCl/BiOCl heterojunction was ascribed to the synergistic effect of the enhanced light absorption and effective photoinduced charge carrier separation and transfer. Moreover, the degradation efficiency of the AgCl/BiOCl heterojunction towards ofloxacin, norfloxacin and Lanasol Red 5B was 73%, 74% and 96%, respectively. The experimental factors for the degradation efficiency of TC were also studied. Furthermore, active species trapping experiments indicated that superoxide radicals (ËO2-) were the main reactive species, and the Z-scheme charge transfer mechanism helped to improve the photocatalytic activity.
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BACKGROUND: Postoperative recurrence of oral cancer is an important factor affecting the prognosis of patients. Artificial intelligence is used to establish a machine learning model to predict the risk of postoperative recurrence of oral cancer. METHODS: The information of 387 patients with postoperative oral cancer were collected to establish the multilayer perceptron (MLP) model. The comprehensive variable model was compared with the characteristic variable model, and the MLP model was compared with other models to evaluate the sensitivity of different models in the prediction of postoperative recurrence of oral cancer. RESULTS: The overall performance of the MLP model under comprehensive variable input was the best. CONCLUSION: The MLP model has good sensitivity to predict postoperative recurrence of oral cancer, and the predictive model with variable input training is better than that with characteristic variable input.
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Inteligência Artificial , Neoplasias Bucais , Humanos , Redes Neurais de Computação , Aprendizado de Máquina , Neoplasias Bucais/cirurgiaRESUMO
BACKGROUND: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers. RESULTS: L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability. CONCLUSIONS: The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.
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Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures. Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events. Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis. Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage.
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Active-screen plasma (ASP) has attracted much attention as a versatile and powerful surface engineering method owing to its simple setup, low temperature, eco-friendliness, treatment uniformity, ability to deposit nano/microparticles with sputtering targets, and capability for controlling the chemical composition and morphology of the deposition layer. Recent investigations have shown that ASP technology has been used to treat various electrode materials for excellent electrochemical performance. This work demonstrates the feasibility of ASP technology to construct an artificial alloy layer on host materials and serve as promising Zn anode supports. We reveal the effect of some controllable or measurable variables on the formed alloy layer and discuss the core process of ASP-enabled metal alloying. Attractively, a stable and uniform Cu5Zn8 alloy layer with good zincophilic can effectively reduce the energy barrier of Zn nucleation and guide uniform Zn nucleation, which alleviates the dendritic growth during Zn deposition. Consequently, the Cu5Zn8-modified Cu host as the Zn anode support displays a high Coulombic efficiency of 99.5%, a lower overpotential of 45 mV, and a longer cycling life over 330 h. The assembled full cells deliver an exceptional capacity of 114 mA h g-1 after 500 cycles with a capacity retention of 68%. This work provides an idea for constructing a stable Zn deposition interface and promotes the development of ASP technology.
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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.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Prognóstico , Microambiente Tumoral , Antígenos CD79RESUMO
When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length-width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily.
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Both covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) have been tried in the palliation of malignant distal biliary strictures by means of endoscopic retrograde cholangiopancreatography (ERCP); however, the comparison of efficacy and safety between them remains contested. To the best of our knowledge, no similar studies have assessed this in the Chinese population. In the present study, the clinical and endoscopic data of 238 patients (CSEMSs, n=55; USEMSs, n=183) with malignant distal biliary strictures from 2014 to 2019 were collected. The efficacy indicated by mean stent patency, stent patency rate, mean patient survival time and survival rate, and the safety indicated by adverse events after CSEMS or USEMS placement were retrospectively analyzed and compared. The mean stent patency time was significantly longer in the CSEMSs group than that in the USEMSs group (262.8±195.3 days vs. 169.5±155.7 days, P=0.002). The mean patient survival time was significantly longer in the CSEMSs group than that in the USEMSs group (273.9±197.6 days vs. 184.9±167.6 days, P=0.003). The stent patency rate and patient survival rate were significantly higher in the CSEMSs group than those in the USEMSs group at 6 and 12 months, but not at 1 and 3 months. There was no significant difference in stent dysfunction and adverse events between the two groups, although post-ERCP pancreatitis (PEP) occurred more frequently in the CSEMSs group than in the USEMSs group (18.1% vs. 8.8%, P=0.049). In conclusion, CSEMSs were better than USEMSs for malignant distal biliary strictures in terms of stent patency time and patient survival time as well as stent patency rate and patient survival rate in the long term (>6 months). Adverse events in the two groups occurred at a similar rate, although the incidence of PEP was higher in the CSEMSs group.
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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.