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The appropriate degradation characteristics of polydioxanone (PDO) are necessary for the safety and effectiveness of stents. This study aimed to investigate the degradation of PDO weaving tracheal stents (PW stents)in vitroandin vivo. The degradation solution ofS. aureus(SAU),E. coli(ECO),P. aeruginosa(PAE), and control (N) were prepared, and the PW stents were immersed for 12 weeks. Then, the radial support force, weight retention, pH, molecular structure, thermal performance, and morphology were determined. Furthermore, the PW stents were implanted into the abdominal cavity of rabbits, and omentum was embedded. At feeding for 16 weeks, the mechanical properties, and morphology were measured. During the first 8 weeks, the radial support force in all groups was progressively decreased. At week 2, the decline rate of radial support force in the experimental groups was significantly faster compared to the N group, and the difference was narrowed thereafter. The infrared spectrum showed that during the whole degradation process, SAU, ECO and PAE solution did not lead to the formation of new functional groups in PW stents.In vitroscanning electron microscope observation showed that SAU and ECO were more likely to gather and multiply at the weaving points of the PW stents, forming colonies.In vivoexperiments showed that the degradation in the concavity of weaving points of PW stents was more rapid and severe. The radial support loss rate reached more than 70% at week 4, and the radial support force was no longer measurable after week 8. In omentum, multinuclear giant cells and foreign giant cells were found to infiltrate. PW stents have good biocompatibility. The degradation rate of PW stents in the aseptic conditionsin vivowas faster than in the bacteriological environmentin vitro.
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Ensayo de Materiales , Polidioxanona , Stents , Tráquea , Animales , Polidioxanona/química , Conejos , Materiales Biocompatibles/química , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Concentración de Iones de Hidrógeno , EpiplónRESUMEN
This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Neoadyuvante , Piridinas , Humanos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Adulto , Estadificación de Neoplasias , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidoresRESUMEN
PURPOSE: To explore the effect of dural puncture epidural (DPE) block technique on fetal heart rate variability (HRV) during labor analgesia. METHODS: Sixty full-term primiparas who were in our hospital from April 2021 to October 2021 were selected and randomized into epidural analgesia (CEA) and dural puncture epidural analgesia (DPEA) groups (n = 30). After a successful epidural puncture, routine epidural catheter (EC) was performed in CEA group, and spinal anesthesia needle (as an EC) was used to puncture the dura mater to subarachnoid space in DPE group. Anesthetics were injected through EC. The time when the temperature sensation plane reached T10 (W1) and visual analog pain score (VAS), baseline heart rate score, amplitude variation score, cycle variation score, acceleration score, deceleration score, and total score of the first contraction after W1 were recorded. Apgar scores at 1 min, 5 min, and 10 min of neonates after delivery were recorded. RESULTS: The onset time of anesthesia in CEA group was significantly longer than that in DPEA group (p < .05). However, there are no significant differences in W1, VAS, baseline heart rate score, amplitude variation score, cycle variation score, acceleration score, deceleration score, and total score of the first contraction after W1 between the two groups (p > .05). Moreover, the Apgar scores at 1 min, 5 min and 10 min of neonates after delivery were not notably different between the two groups (p > .05). CONCLUSION: Compared with CEA, DPE block technique in labor analgesia relieves maternal pain without adverse effects on fetal HRV and newborns.
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Analgesia Epidural , Analgesia Obstétrica , Frecuencia Cardíaca Fetal , Humanos , Femenino , Embarazo , Frecuencia Cardíaca Fetal/efectos de los fármacos , Frecuencia Cardíaca Fetal/fisiología , Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgesia Obstétrica/efectos adversos , Adulto , Recién Nacido , Puntaje de Apgar , Dimensión del Dolor , Duramadre , Trabajo de Parto/fisiología , Trabajo de Parto/efectos de los fármacosRESUMEN
Fe-based metal-organic frameworks (MOFs) have good photocatalytic performance, environmental friendliness, low cost, and abundance. However, their applications are limited by low water stability, particularly in the presence of light irradiation and oxidizing agents. In this study, we present a MIL-53(Fe)-based MOF using 1,4-naphthalene dicarboxylic (1,4-NDC) and 1,4-benzenedicarboxylic (H2BDC) acid co-ligands, denoted MIL-53(Fe)-Nx, where Nx represents the ratio of 1,4-NDC. This MOF exhibits high water stability and good photocatalytic activity because of the hydrophobicity of naphthalene. The removal and mineralization rates for 100 mg/L 2,4-dichlorophenol reached 100% and 22%, respectively, within 60 min. After three cycles of use, the Fe leached into the solution from the catalysts was significantly lower than the maximum permissible limit indicated in the European Union standard. Of note, 1,4-NDC can be used to make a rigid MOF, thereby improving the crystallinity, porosity, and hydrophobicity of the resultant materials. It also significantly reduced the bandgap energy and improved the charge separation efficiency of the catalysts. This study provides a route to enhance the water stability of Fe-based MOFs via a mixed-ligand strategy to expand their applications in pollutant control.
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Clorofenoles , Hierro , Estructuras Metalorgánicas , Contaminantes Químicos del Agua , Estructuras Metalorgánicas/química , Clorofenoles/química , Catálisis , Contaminantes Químicos del Agua/química , Hierro/química , Agua/química , LigandosRESUMEN
Purpose: Esophageal squamous cell carcinoma (ESCC) is a disease with a high incidence rate and high mortality worldwide. The Never in Mitosis A (NIMA) family member NIMA-related kinase 2 (NEK2) plays an important role in mitosis. However, the role of NEK2 in the pathogenesis of ESCC remains unclear. Patients and methods: The expression and function of NEK2 in TCGA and GEO data sets were analyzed by bioinformatics. We verified the expression of NEK2 in ESCC tissues and cell lines by Western blotting and immunohistochemical methods and further explored the relationship between tumor stage and NEK2 expression. The differences in NEK2 expression and survival in patients with EC were verified by bioinformatics analysis. ESCC cell lines with stable knockdown of NEK2 were established by lentivirus-mediated shRNA delivery. The effects of NEK2 on ESCC cells were analyzed on the cytological level with assays including CCK-8, EdU, cell scratch, Transwell migration and invasion, colony formation, flow cytometry and apoptosis assays. Tumor growth was measured in a mouse xenograft model. Results: We found that NEK2 is highly expressed in ESCC tissues and ESCC cells and that the high expression of NEK2 is associated with poor tumor healing. Knockdown of the NEK2 gene inhibits the migration, proliferation, invasion and cell cycle of ESCC cells. Biologic analysis shows that NEK2 is involved in biological processes such as progression and apoptosis of esophageal cancer, and is related to E2F.Mechanistically, NEK2 knockdown decreases the expression levels of E2F1 and IGF2. NEK2 competes with the transcription factor E2F1 to bind CDC20, resulting in decreased degradation and increased expression of E2F1. IGF2 expression is also increased, which promotes the expression of thymidylate synthase, further promoting the drug resistance of ESCC cells. NEK2 is associated with immune infiltration in esophageal cancer. Conclusion: NEK2 is highly expressed in ESCC and can promote the migration, proliferation and invasion of ESCC cells. NEK2 mediates ESCC immunotherapy.
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STUDY OBJECTIVE: To investigate whether the addition of S-ketamine to patient-controlled hydromorphone analgesia decreases postoperative moderate-to-severe pain and improves the quality of recovery (QoR) in patients undergoing thoracoscopic lung surgery. DESIGN: Single-center prospective randomized double-blinded controlled trial. SETTING: Tertiary university hospital. PATIENTS: 242 patients undergoing thoracoscopic lung surgery. INTERVENTIONS: Patients were randomized to receive intravenous patient-controlled analgesia (IV-PCA) with hydromorphone alone or hydromorphone combined with S-ketamine (0.5 mg/kg/48 h, 1 mg/kg/48 h, or 2 mg/kg/48 h). MEASUREMENTS: Primary outcome was proportion of patients with moderate-to-severe pain. (numerical rating scale [NRS] pain scores ≥4 when coughing) within 2 days after surgery. Postoperative QoR scores and other prespecified outcomes were also recorded. MAIN RESULTS: Of 242 enrolled patients, 220 were included in the final analysis. The results demonstrated that the incidence of postoperative moderate-to-severe pain was significantly different between the hydromorphone group and combined S-ketamine group (absolute difference, 27.9%; 95% confidence interval [CI], 11.7% to 42.1%; P < 0.001). Patients who received S-ketamine had lower NRS pain scores at rest and when coughing on postoperative day 1 (POD1; median difference 1 and 1, P < 0.001) and postoperative day 2 (POD2; median difference 1 and 1, P < 0.001). The QoR-15 scores were higher in the combined S-ketamine group on POD1 (mean difference 6, P < 0.001) and POD2 (mean difference 6, P < 0.001) than in the hydromorphone group. A higher dose of S-ketamine was associated with deeper sedation. No differences were detected in the other safety outcomes. CONCLUSIONS: Addition of S-ketamine to IV-PCA hydromorphone significantly reduced the incidence of postoperative moderate-to-severe pain and improved the QoR in patients undergoing thoracoscopic lung surgery. TRIAL REGISTRATION: Chinese Clinical Trail Register (identifier: ChiCTR2200058890).
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Analgesia Controlada por el Paciente , Hidromorfona , Humanos , Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides/efectos adversos , Hidromorfona/efectos adversos , Pulmón/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Método Doble CiegoRESUMEN
The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting the need for highly effective biomarkers and reproducible experimental models. Current immunotherapy biomarkers encompass surface protein markers such as PD-L1, genetic features such as microsatellite instability, tumor-infiltrating lymphocytes, and biomarkers in liquid biopsy such as circulating tumor DNAs. Experimental models, ranging from 3D in vitro cultures (spheroids, submerged models, air-liquid interface models, organ-on-a-chips) to advanced 3D bioprinting techniques, have emerged as valuable platforms for cancer immunology investigations and immunotherapy biomarker research. By preserving native immune components or coculturing with exogenous immune cells, these models replicate the tumor microenvironment in vitro. Animal models like syngeneic models, genetically engineered models, and patient-derived xenografts provide opportunities to study in vivo tumor-immune interactions. Humanized animal models further enable the simulation of the human-specific tumor microenvironment. Here, we provide a comprehensive overview of the advantages, limitations, and prospects of different biomarkers and experimental models, specifically focusing on the role of biomarkers in predicting immunotherapy outcomes and the ability of experimental models to replicate the tumor microenvironment. By integrating cutting-edge biomarkers and experimental models, this review serves as a valuable resource for accessing the forefront of cancer immunology investigation.
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[This corrects the article DOI: 10.7150/thno.30726.].
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Hepatitis B is an infectious disease cause by the hepatitis B virus (HBV). In recent years, HBV-DNA level clinically gets more attention for its detailed information than other serological markers. Unfortunately, common clinical method for HBV-DNA level detection is limited for its hours consuming. This study combined infrared spectroscopy with machine learning to investigate the feasibility of near-infrared (NIR) and mid-infrared (MIR) spectra for rapid detection of HBV-DNA level. Based on partial least squares-discriminant analysis (PLS-DA) modeling method, the optimal NIR and MIR models and traditional data fusion models were constructed, respectively. Considering inequal weight between interval and point data in machine learning, interval-point data fusion method was used to compare with other traditional date fusion methods. The results of the study illustrate that interval-point data fusion of NIR and MIR spectra combined with PLS-DA modeling can provide a rapid method for HBV-DNA level detection.
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Virus de la Hepatitis B , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , ADN Viral , Espectrofotometría Infrarroja , Análisis Discriminante , Análisis de los Mínimos CuadradosRESUMEN
1,2-Dichloroethane (1,2-DCA) is a common compound found in groundwater contaminated with organics. This compound is difficult to remove from groundwater and has the potential to inflict significant harm on human health and the environment. This study used sodium persulfate (Na2S2O8) activated by sodium hydroxide (NaOH) to remove 1,2-DCA from aqueous solutions. Density functional theory was employed to calculate the potential energy surface of the reactants, intermediates, transient states, and products to thoroughly analyze the degradation pathways. The computations were performed in combination with in situ remediation of a 1,2-DCA plume from a point source to verify the industrial applicability of the technology. The results showed the 1,2-DCA removal efficiency was impacted considerably by the Na2S2O8 dosage and the dosing sequence of Na2S2O8 and NaOH, with the mean removal ratio reaching 96.24%. A free radical reaction was the main pathway of 1,2-DCA degradation; superoxide radical (O2â¢-) existed stably and played a key role in the reaction, and the main transformation proceeded via a vinyl chloride intermediate. The maximum removal of 1,2-DCA reached 91.79% in the in situ remediation. The developed technology exhibits important advantages in enabling flexible control over chemical dosages, long durations of effective activity, and rapid full-cycle remediation.
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Agua Subterránea , Contaminantes Químicos del Agua , Humanos , Hidróxido de Sodio , Contaminantes Químicos del Agua/análisis , Agua Subterránea/química , Sulfatos/química , Cinética , Oxidación-ReducciónRESUMEN
This paper presents a piezoresistive differential pressure sensor based on a silicon-on-insulator (SOI) structure for low pressure detection from 0 to 30 kPa. In the design phase, the stress distribution on the sensing membrane surface is simulated, and the doping concentration and geometry of the piezoresistor are evaluated. By optimizing the process, the realization of the pressure sensing diaphragm with a controllable thickness is achieved, and good ohmic contact is ensured. To obtain higher sensitivity and high temperature stability, an SOI structure with a 1.5 µm ultra-thin monocrystalline silicon layer is used in device manufacturing. The device diaphragm size is 700 µm × 700 µm × 2.1 µm. The experimental results show that the fabricated piezoresistive pressure sensor has a high sensitivity of 2.255 mV/V/kPa and a sensing resolution of less than 100 Pa at room temperature. The sensor has a temperature coefficient of sensitivity (TCS) of -0.221 %FS/°C and a temperature coefficient of offset (TCO) of -0.209 %FS/°C at operating temperatures ranging from 20 °C to 160 °C. The reported piezoresistive microelectromechanical systems (MEMS) pressure sensors are fabricated on 8-inch wafers using standard CMOS-compatible processes, which provides a volume solution for embedded integrated precision detection applications of air pressure, offering better insights for high-temperature and miniaturized low-pressure sensor research.
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This paper presents a novel bimorph Piezoelectric Micromachined Ultrasonic Transducer (PMUT) fabricated with 8-inch standard CMOS-compatible processes. The bimorph structure consists of two layers of 20% scandium-doped aluminum nitride (Sc0.2Al0.8N) thin films, which are sandwiched among three molybdenum (Mo) layers. All three Mo layers are segmented to form the outer ring and inner plate electrodes. Both top and bottom electrodes on the outer ring are electrically linked to the center inner plate electrodes. Likewise, the top and bottom center plate electrodes are electrically connected to the outer ring in the same fashion. This electrical configuration maximizes the effective area of the given PMUT design and improves efficiency during the electromechanical coupling process. In addition, the proposed bimorph structure further simplifies the device's electrical layout with only two-terminal connections as reported in many conventional unimorph PMUTs. The mechanical and acoustic measurements are conducted to verify the device's performance improvement. The dynamic mechanical displacement and acoustic output under a low driving voltage (1 Vpp) are more than twice that reported from conventional unimorph devices with a similar resonant frequency. Moreover, the pulse-echo experiments indicate an improved receiving voltage of 10 mV in comparison with the unimorph counterpart (4.8 mV). The validation of device advancement in the electromechanical coupling effect by using highly doped ScAlN thin film, the realization of the proposed bimorph PMUT on an 8-inch wafer paves the path to production of next generation, high-performance piezoelectric MEMS.
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This research explored the feasibility of early warning and diagnostic visualization of Sclerotinia infected tomato by using hyperspectral imaging technology. Healthy tomato plants and tomato plants with Sclerotinia sclerotiorum were cultivated, and hyperspectral images at 400-1000 nm were collected from healthy and infected tomato leaves at 1, 3, 5, and 7 days of incubation. After preprocessing the spectra with first derivative (FD), second derivative (SD), standard normal variant (SNV), and multiplicative scatter correction (MSC) partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM) were used to construct tomato sclerotinia identification model and select the best preprocessing method. On this basis, two band screening methods, competitive adaptive reweighted sampling (CARS) and successive projections algorithm (SPA), were introduced to reduce data redundancy and improve the model's prediction accuracy. The results showed that the accuracy of the validation sets and operation speed of the CARS-PLS and CARS-SVM models were 87.88% and 1.8 s, and 87.95% and 1.78 s, respectively. The experiment was based on the SNV-CARS-SVM prediction model combined with image processing, spectral extraction, and visualization analysis methods to create diagnostic visualization software, which opens a new avenue to the implementation of online monitoring and early warning system for sclerotinia infected tomato.
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Solanum lycopersicum , Imágenes Hiperespectrales , Estado de SaludRESUMEN
This paper introduces a novel nondestructive wafer scale thin film thickness measurement method by detecting the reflected picosecond ultrasonic wave transmitting between different interfacial layers. Unlike other traditional approaches used for thickness inspection, this method is highly efficient in wafer scale, and even works for opaque material. As a demonstration, we took scandium doped aluminum nitride (AlScN) thin film and related piezoelectric stacking layers (e.g. Molybedenum/AlScN/Molybdenum) as the case study to explain the advantages of this approach. In our experiments, a laser with a wavelength of 515 nm was used to first measure the thickness of (1) a single Molybdenum (Mo) electrode layer in the range of 100-300 nm, and (2) a single AlScN piezoelectric layer in the range of 600-1000 nm. Then, (3) the combined stacking layers were measured. Finally, (4) the thickness of a standard piezoelectric composite structure (Mo/AlScN/Mo) was characterized based on the conclusions and derivation extracted from the aforementioned sets of experiments. This type of standard piezoelectric composite has been widely adopted in a variety of Micro-electromechanical systems (MEMS) devices such as the Piezoelectric Micromachined Ultrasonic Transducer (PMUT), the Film Bulk Acoustic Resonator (FBAR), the Surface Acoustic Wave (SAW) and more. A comparison between measurement data from both in-line and off-line (using Scanning Electron Microscope) methods was conducted. The result from such in situ 8-inch wafer scale measurements was in a good agreement with the SEM data.
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To monitor environmental water pollution effectively and meet human water needs, it is crucial to develop a fast, simple, and accurate method for monitoring chemical oxygen demand (COD) in various water systems. In this study, COD prediction models for different water systems were developed by combining near-infrared (NIR) spectroscopy with partial least squares regression (PLSR). Samples of wastewater, surface water, and seawater were collected from Guangzhou, Guangdong Province, China. Three pretreatment methods were used to preprocess the spectra in order to improve the accuracy and minimalism of the model. We investigate the performance of two variable selection algorithms, namely, binary gray wolf optimization (BGWO) and competitive adaptive reweighting sampling (CARS). The results show that both BGWO and CARS improved the performance of the model in terms of higher accuracy and less wavelength input; both of the combined model performances were better than that of PLSR alone, and CARS-PLSR achieved the best results. Using CARS-PLSR, surface water, wastewater, and seawater model inputs were reduced by 96 %, 96 %, and 82 % as compared to the PLSR results, respectively, and the testing sets R2 reached 0.860, 0.815, and 0.692, respectively. The spectral variable selection algorithm could identify the important spectral variables between COD content and NIR spectra in three water systems, thereby improving the accuracy and simplicity of the PLSR model for COD prediction. Our results have important practical value for predicting COD content in different water systems by NIR spectroscopy.
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Espectroscopía Infrarroja Corta , Agua , Algoritmos , Análisis de la Demanda Biológica de Oxígeno , Humanos , Análisis de los Mínimos Cuadrados , Espectroscopía Infrarroja Corta/métodos , Aguas ResidualesRESUMEN
Esophageal cancer is a lethal disease, and emerging evidence has shown that microRNAs are involved in its development, progression, and clinical outcome. MicroRNAs are potential biomarkers for esophageal squamous cell carcinoma (ESCC), and may be useful in advanced RNA therapy for ESCC. This study was conducted to evaluate the molecular mechanism of miR-4739 in ESCC. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure RNA and protein levels. Transwell assay, Cell Counting Kit-8 assay, cytometry analysis, and human umbilical vein endothelial cell tube formation assay were conducted to determine the molecular function of miR-4739 in ESCC. Potential targets of miR-4739 were predicted using bioinformatics tools and confirmed in ESCC cells using a luciferase reporter and RNA pulldown assay. Finally, we performed immunohistochemistry to evaluate the effects of administering agomir-4739 to a mouse model of ESCC. MiR-4739 expression was downregulated in ESCC tissues and cells. MiR-4739 overexpression inhibited cell proliferation, migration, and invasion, and promoted apoptosis of ESCC cells. Furthermore, vascular endothelial growth factor A expression was downregulated by miR-4739 mimics in ESCC cells. MiR-4739 negatively regulated homeobox C10 expression. Additionally, agomir-4739 inhibited tumor growth and angiogenesis in vivo. We demonstrated that miR-4739 overexpression exerted an inhibitory effect on ESCC cells by preventing the expression of homeobox C10 via the vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway, indicating the potential of this microRNA as a treatment target in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Regulación Neoplásica de la Expresión Génica , Genes Homeobox , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Background: Cough is one of the most common complications of early-stage non-small cell lung cancer (NSCLC) after video-assisted thoracoscopic surgery (VATS). The vagus nerve plays an important role in pulmonary inflammation and the cough reflex. In this study, we attempted to reduce the incidence of postoperative chronic cough and other complications by preserving the pulmonary vagus nerve branches. Patients and Methods: This study was a randomized controlled double-blinded trial of subjects and observers. A total of 158 NSCLC patients were enrolled. We randomly assigned 79 patients to Group A (pulmonary branch of vagus nerve preservation group) and 79 cases to Group B (conventional surgical treatment group). In the final analysis, 72 patients from Group A and 69 patients from Group B were included. The main outcome measure of the study was the occurrence of CAP or other postoperative complications within five weeks. This trial was registered with ClinicalTrials.gov (number NCT03921828). Results: There was no significant difference in preoperative general clinical data between the two groups. No death during the perioperative period occurred in either of the two groups. There was no significant difference between the two groups in operation time, intraoperative bleeding, number of lymph nodes sent for examination, number of cases transferred to ICU after operation, postoperative catheterization time, or postoperative hospital stay (P>0.05). There was no significant difference in other pulmonary and cardiovascular complications between the two groups, including pulmonary infection (2.78% vs. 8.70%, P = 0.129), atelectasis (1.39% vs. 0%, P = 0.326), pleural effusion (2.78% vs. 1.45%, P = 0.585), persistent pulmonary leakage (2.78% vs. 2.90%, P = 0.965), arrhythmia (2.78% vs. 1.45%, P = 0.585), and heart failure (0% vs. 1.45%, P = 0.305). The incidence of CAP in Group A was significantly lower than that in Group B (13.89% vs. 30.43%, P = 0.018). The LCQ-MC scores in Group A were significantly higher than those in Group B at two and five weeks after operation (P<0.05). Univariate and multivariate analysis showed that the risk factors for postoperative CAP were surgical side (right lung), surgical lung lobe (upper lobe), preservation of pulmonary branch of the vagus nerve during operation, and duration of anesthesia. Conclusions: Preserving the pulmonary vagus nerve branches during VATS in patients with stage IA1-2 NSCLC can reduce the incidence of postoperative CAP.
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Lung adenocarcinoma (LUAD) is associated with a poor prognosis due to early metastasis to distant organs. TGF-ß potently induces epithelial-to-mesenchymal transition (EMT) and promotes invasion and metastasis of cancers. However, the mechanisms underlying this alteration are largely unknown. PTBP3 plays a critical role in RNA splicing and transcriptional regulation. Although accumulating evidence has revealed that PTBP3 exhibits a pro-oncogenic role in several cancers, whether and how PTBP3 mediates TGF-ß-induced EMT and metastasis in LUAD remains unknown. The expression levels and prognostic value of PTBP3 were analyzed in human LUAD tissues and matched normal tissues. siRNAs and lentivirus-mediated vectors were used to transfect LUAD cell lines. Various in vitro experiments including western blot, qRT-PCR, a luciferase reporter assay, chromatin immunoprecipitation (ChIP), transwell migration and invasion assay and in vivo metastasis experiment were performed to determine the roles of PTBP3 in TGF-ß-induced EMT and metastasis. PTBP3 expression was significantly upregulated in patients with LUAD, and high expression of PTBP3 indicated a poor prognosis. Intriguingly, we found that PTBP3 expression level in LUAD cell lines was significantly increased by exogenous TGF-ß1 in a Smad-dependent manner. Mechanistically, p-Smad3 was recruited to the PTBP3 promoter and activated its transcription. In turn, PTBP3 knockdown abolished TGF-ß1-mediated EMT through the inhibition of Smad2/3 expression. Furthermore, PTBP3 overexpression increased lung and liver metastasis of LUAD cells in vivo. PTBP3 is indispensable to TGF-ß-induced EMT and metastasis of LUAD cells and is a novel potential therapeutic target for the treatment of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteína de Unión al Tracto de Polipirimidina , Factor de Crecimiento Transformador beta1 , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Transición Epitelial-Mesenquimal , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
BACKGROUND AND AIMS OF STUDY: Transcatheter mitral valve implantation (TMVI) is a promising and minimally invasive treatment for high-risk mitral regurgitation. We aimed to investigate the feasibility of a novel self-expanding valved stent for TMVI via apical access. METHODS: We designed a novel self-expanding mitral valve stent system consisting of an atrial flange and saddle-shaped ventricular body connected by two opposing anchors and two opposing extensions. During valve deployment, each anchor was controlled by a recurrent string. TMVI was performed in 10 pigs using the valve prosthesis through apical access to verify technical feasibility. Echocardiography and ventricular angiography were used to assess hemodynamic data and valve function. Surviving pigs were killed 4 weeks later to confirm stent deployment. RESULTS: Ten animals underwent TMVI using the novel mitral valve stent. Optimal valve deployment and accurate anatomical adjustments were obtained in nine animals. Implantation failed in one case, and the animal died 1 day later due to stent mismatch. After stent implantation, the hemodynamic parameters of the other animals were stable, and valve function was normal. The mean pressure across the mitral valve and left ventricular outflow tract were 2.98 ± 0.91 mmHg and 3.42 ± 0.66 mmHg, respectively. Macroscopic evaluation confirmed the stable and secure positioning of the stents. No obvious valve displacement, embolism, or paravalvular leakage was observed 4 weeks postvalve implantation. CONCLUSIONS: This study demonstrated that the novel mitral valve is technically feasible in animals. However, the long-term feasibility and durability of this valved stent must be improved and verified.