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The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family.
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Controllable assembly of DNA nanostructure provides a powerful way for quantitative analysis of various targets including nucleic acid molecules. In this study, we have designed detachable DNA nanostructures at electrochemical sensing interface and constructed a ligation chain reaction (LCR) strategy for amplified detection of miRNA. A three-dimensional DNA triangular prism nanostructure is fabricated to provide suitable molecule recognition environment, which can be further regenerated for additional tests via convenient pH adjustment. Target triggered LCR is highly efficient and specific towards target miRNA. Under optimal experimental conditions, this approach enables ultrasensitive exploration in a wide linear range with a single-base resolution. Moreover, it shows excellent performances for the analysis of cell samples and clinical serum samples.
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Técnicas Biosensibles , ADN , MicroARNs , Nanoestructuras , MicroARNs/sangre , MicroARNs/análisis , Técnicas Biosensibles/métodos , Humanos , ADN/química , Nanoestructuras/química , Técnicas Electroquímicas/métodos , Reacción en Cadena de la Ligasa/métodos , Límite de DetecciónRESUMEN
Nucleic acid detection plays a crucial role in various aspects of health care, necessitating accessible and reliable quantification methods, especially in resource-limited settings. This work presents a simplified electrochemical approach for end-point yet quantitative nucleic acid detection. By elevating the concentration of redox species and choosing potential as the signals, we achieved enhanced signal robustness, even in the presence of interfering substances. Leveraging this robustness, we accurately measured pH-induced redox potential changes in methylene blue solution for end-point nucleic acid detection after loop-mediated isothermal amplification (LAMP). Our method demonstrated quantitative detection of the SARS-CoV-2 N gene and human ATCB gene and successful discrimination of the human BRAF V600E mutation, comparable in sensitivity to commercial kits. The developed user-friendly electrochemical method offers a simplified and reliable approach for end-point yet quantitative detection of nucleic acids, potentially expanding the benefits of nucleic acid testing in resource-limited settings.
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Técnicas Electroquímicas , Técnicas de Amplificación de Ácido Nucleico , SARS-CoV-2 , Técnicas Electroquímicas/métodos , Humanos , SARS-CoV-2/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Proteínas Proto-Oncogénicas B-raf/genética , COVID-19/diagnóstico , COVID-19/virología , Azul de Metileno/química , Mutación , Oxidación-Reducción , Técnicas de Diagnóstico Molecular/métodos , Configuración de Recursos LimitadosRESUMEN
Metal-organic frameworks (MOFs) with fit ligands and metals can be integrated into electrochemical biosensors for the detection of various biomolecules. In this study, we have synthesized novel magnetic MOF composites as electrocatalysts and constructed a novel biosensor for electrochemical detection of dopamine. The composites named Fe3O4@ZIF-8@AuNPs-COOH are synthesized through layer-by-layer assembly. They exhibit excellent stability and cooperative catalytic activity. In addition, green recycling is readily achieved through magnetizing/demagnetizing the electrode. The large specific surface area and ordered porous structures of the magnetic MOFs ensure good dispersion of gold nanoparticles, while the carboxyl group efficiently shields other redox-active interfering substances. The proposed electrochemical biosensor accomplishes the sensitive detection of dopamine in human serums and living cells. This study broadens the application of MOFs in electrochemical biosensing, validates the feasibility of biosensors for in vivo analysis, and provides new insights into green sensing.
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Técnicas Biosensibles , Dopamina , Técnicas Electroquímicas , Estructuras Metalorgánicas , Dopamina/análisis , Dopamina/sangre , Dopamina/química , Técnicas Biosensibles/métodos , Estructuras Metalorgánicas/química , Humanos , Catálisis , Oro/química , Tamaño de la Partícula , Propiedades de Superficie , Nanopartículas del Metal/química , ElectrodosRESUMEN
Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.
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Antibacterianos , Berberina , Ácido Clorogénico , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Nanopartículas , Berberina/farmacología , Berberina/química , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Animales , Nanopartículas/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Culter alburnus (topmouth culter)is an economically valuable freshwater fish. However, its insufficient tolerance to dissolved oxygen (DO) and ammonia nitrogen (AN) hinders its industrialisation. 360 experimental fish (4.87 ± 1.10 g) were placed in breathing chambers (oxygen level was 0.70-6.50 mg/L) or water tanks (control AN, 0 mg/L; low AN, 8 mg/L; high AN, 16 mg/L). This study analysed the effects of DO and AN on C. alburnus at physiological, biochemical, and molecular levels. (1) Physiology level: the floating point, coma critical point, and coma point at 20 °C group were significantly higher than those at 30 °C. The oxygen consumption rate of C. alburnus at 20 °C, 25 °C, and 30 °C was (256.65 ± 25.87), (470.47 ± 83.84), and (520.87 ± 55.40) mg/kg.h. The LC50 of AN after 96 h was 24.13 mg/L, and the safe concentration was 2.41 mg/L. The survival rate in the high AN group was significantly lower than that in the other two groups. (2) Biochemistry level: The change curves of antioxidant enzyme activity in the liver tissue under hypoxic stress reached a maximum at 12 h and then decreased. In addition, the increase and decrease in enzyme activity (except malondialdehyde) in the high AN group was lower than that in the low AN group. (3) Molecular level: the angiotensin-converting enzyme and carboxypeptidase genes were the major differentially expressed genes (DEGs) in hypoxic stress, and the DEGs were mainly enriched in the ABC transporter signal transduction pathway. In addition, the serum/glucocorticoid-regulated kinase, stearoyl-CoA desaturase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes were among the major DEGs under high AN stress. The DEGs were mainly enriched in steroid biosynthesis or glycine, serine, and threonine metabolism transporter signal transduction pathways. In summary, it is necessary to focus on the DO and AN during C. alburnus breeding.
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Photo-mineralization of microplastics under mild conditions has emerged as a promising solution to plastic waste disposal. However, the inadequate contact between oxygen, water-insoluble polyolefin microplastics, and photocatalysts remains a critical issue. In this study, a TiO2 hierarchical porous layer (TiO2-HPL) photocatalyst is presented to establish air-plastic-solid triphase interfaces for the photothermal mineralization of polyolefins. The wettability of the TiO2-HPL-based triphase interface is finely controlled from plastophobic to plastophilic. High-resolution imaging and finite element simulation demonstrate the significance of a semiwetting state in achieving multidirectional oxygen diffusion through the hierarchical pore structure while maintaining sufficient contact between the plastic phase and photocatalysts. For low-density polyethylene, the TiO2-HPL achieves a photothermal mineralization rate of 5.63 mmol g-1 h-1 and a conversion of 26.3% after 20 h of continuous irradiation. Additionally, the triphase photocatalytic system with semiwetting gas-plastic-solid interfaces shows good universality for various polyolefin reagents and products, illustrating its potential in achieving efficient photothermal mineralization of non-degradable microplastics.
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Nitrate accumulation in the soil profile in the intensive agricultural region has been widely concerned in the world. However, the changes in nitrate accumulation characteristics caused by climate change, such as extremely high precipitation, are not well quantified, particularly for the regions with thick unsaturated zones. Here, we resampled the soil profiles taken in normal year (2020) after extreme precipitation year (2021) (>800 cm) in three regions in the southern Loess Plateau (LP) with three different water managements including rainfed orchards (n = 10), well-irrigated orchards (n = 4) and canal-irrigated orchards (n = 8). The accumulation amounts, peak depths, and accumulation depths of nitrate soil profiles of the different regions of two years were compared. The results showed that average nitrate accumulation in normal year at the rainfed region (800-cm depth), well-irrigated region (800-cm depth) and canal-irrigated region (1400-cm depth) were 5995 kg N ha-1, 9765 kg N ha-1, and 19,608 kg N ha-1, respectively. Compared with 2020, extreme precipitation in 2021 led to 56-91% reductions (2060-3702 kg N ha-1) in nitrate accumulation in 0-200 cm soil layer, and average nitrate leaching into the aquifer was >1390 kg N ha-1 in the canal-irrigated region. Average migration depths of nitrate peak in rainfed, well-irrigated and canal-irrigated regions were 92 cm, 115 cm, and 188 cm, respectively; as for nitrate accumulation depths, they were 10 cm, 80 cm and 108 cm, respectively. Vertically, the dried soil layer and paleosol layer (high clay content) in the canal-irrigated region significantly hindered nitrate deep migration caused by the extreme precipitation. The result highlights that extreme precipitation significantly accelerated nitrate leaching in the deep soil profiles, and future vulnerability and risk assessment studies must account for the impacts of extreme precipitation on nitrate leaching.
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The CRISPR/Cas12a system is accelerated by glutathione-mediated reduction of MnO2 nanosheets. By monitoring the trans-cleavage of the DNA probe, an electrochemical method for glutathione assay is fabricated, with the detection limit of 3.5 pM. It provides a promising tool for plasma analysis with satisfactory performance, indicating the broad application prospects of this glutathione assay.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Óxidos , Compuestos de Manganeso , Glutatión/análisisRESUMEN
PURPOSE: We studied changes in the choroid, particularly variation in blood flow, during the development of myopia. The hemodynamic mechanism in play remains unclear. We evaluated blood flow by quantitating indocyanine green (ICG) fluorescence in a guinea pig model of form-deprivation myopia. METHODS: Guinea pigs were divided into form-deprivation myopia (FDM) and normal control (NC) groups. Ocular biometric and choroidal hemodynamics parameters were quantitatively derived via ICG imaging, and included the maximal ICG fluorescence intensity (Imax), rising time (Trising), blood flow index (BFI), and mean transit time (MTT). RESULTS: Form deprivation was associated with significant interocular differences in terms of both refractive error and axial length. ICG fluorescence hemodynamic maps of fundal blood flow and vasculature density were evident. In deprived eyes, the fluorescence signals exhibited significantly longer Trising and MTT but lower Imax and BFI than fellow eyes and NC group. The interocular differences in terms of the ocular biometric and hemodynamic parameters were significantly correlated. Hemodynamic analysis of choriocapillaris lobules revealed weakened fluorescence intensity and prolonged arrival and filling times in deprived eyes. Form deprivation reduced the number of lobulated choriocapillaris structures. CONCLUSION: Form-deprivation myopia triggered changes in the hemodynamic and vascular network structures of the choroid and choriocapillaris. The ICG fluorescence imaging/analysis method provides a unique tool for further myopia research.
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Miopía , Errores de Refracción , Animales , Cobayas , Diagnóstico por Imagen , Coroides/diagnóstico por imagen , HemodinámicaRESUMEN
The investigation of the intramolecular charge transfer (ICT) process of gold nanoclusters (AuNCs) is critical to understand the unique features of the nanomaterials, which also benefits their further applications. Herein, 6-methyl-2-thiouracil (CH3-2-TU) and polyvinylpyrrolidone (PVP)-stabilized AuNCs are prepared, and the ICT behaviors are carefully studied. Protonation or deprotonation of the ligands around AuNCs could be used to regulate the ICT state, influencing the electron distribution and band gap. Shifted fluorescence emission phenomena are thus observed, which respond to external pH stimuli. In addition, the AuNCs are developed as color-switchable indicators for the highly sensitive detection of biogenic amines. As a proof of concept, the performance of this strategy in the evaluation of food spoilage by probing pH conditions is validated with satisfactory results. The discoveries in this work offer a convenient route to regulate the optical properties of AuNCs and the design of pH-based sensing applications.
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Low-intensity ultrasound stimulation (LIUS) is an emerging neuro- and vascular-modulation technique. Studies on humans and animals have shown that LIUS could induce changes in neuronal oscillations or blood flow. However, it is still inconclusive whether the hemodynamic response to LIUS is due to neurovascular coupling (NVC), direct ultrasound-vessel interactions, or both. This study aims to detect the direct effect of LIUS on vessels using optical imaging. Fluorescence images with indocyanine green (ICG) were used to identify and quantify the morphological change in the auricle vessels of rats. Diameters of vessels were measured before, during, and post LIUS. The results indicated that LIUS could significantly increase the vessel diameters (p = 0.031). Further exploratory analysis showed that vessel dilation occurred among the majority of randomly selected vessels (i.e., 21/30 animals (70%), dilation: 6.84±1.95µm, 95% CI: [3.02,10.66]), with a significant confounding effect of the vessel size. The results provided indirect evidence for two distinct pathways in LIUS-based neurovascular modulation, i.e., the NVC and the direct ultrasound-vessel interactions.
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Neuronas , Humanos , Ratas , Animales , UltrasonografíaRESUMEN
Here, we demonstrate that high magnetic fields alter the wettability of water and ionic solutions on the single-crystal α-Al2O3. We investigated the relationship between the substrate crystal orientation, material magnetism, liquid conductivity, and the surface contact angle. Applying high magnetic fields decreased the water contact angles on all of the surface orientations studied, and the reduction was larger for more magnetic substrates. For ionic solutions, high magnetic fields increased the contact angle on the (0001) α-Al2O3 surface but decreased the contact angles on the (112Ì 0), (101Ì 0), and (011Ì 2) surfaces. We attribute these orientation-dependent ionic solution responses to competition between the field-induced sample magnetization energy and the Lorentz force acting on the ionic solution. Overall, this work provides new magnetic-field-based strategies for changing the wettability and provides guidelines for fabricating novel microfluidic systems or biointerfaces with in situ magnetic control.
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Nano-impact electrochemistry (NIE) enables simple, rapid, and high-throughput biocoupling and biomolecular recognition. However, the low effective collision frequency limits the sensitivity. In this study, we propose a novel NIE sensing strategy amplified by the CRISPR-responsive DNA hydrogel and cascade DNA assembly. By controlling the phase transition of DNA hydrogel and the self-electrolysis of silver nanoparticles, we can obtain significant electrochemical responses. The whole process includes target miRNA-induced strand displacement amplification, catalytic hairpin assembly, and CRISPR/Cas trans-cutting. Thus, ultrahigh sensitivity is promised. This NIE biosensing strategy achieves a limit of detection as low as 4.21 aM for miR-141 and demonstrates a high specificity for practical applications. It may have wide applicability in nucleic acid sensing and shows great potential in disease diagnosis.
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Técnicas Biosensibles , Nanopartículas del Metal , MicroARNs , Hibridación de Ácido Nucleico , Nanopartículas del Metal/química , Hidrogeles , Técnicas Electroquímicas , Técnicas de Amplificación de Ácido Nucleico , Límite de Detección , Plata/química , ADN/química , MicroARNs/genéticaRESUMEN
An electrochemical sensing approach for ultrasensitive DNA methyltransferase (MTase) activity assay is proposed. After specific cleavage reaction in the presence of a methylated state, strand displacement polymerization (SDP) is initiated in the solution. The product of upstream SDP further triggers downstream SDP, which enriches abundant electrochemical species at the electrode. The whole process is quite convenient with shared enzymes. Due to the cascade signal amplification, ultrahigh sensitivity is promised. Inhibitor screening results are also demonstrated to be good. Besides, target MTase can be accurately determined in human serum samples, confirming excellent practical utility. This work provides a reliable approach for the analysis of MTase activity, which is of vital importance for related biological studies and clinical applications.
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Técnicas Biosensibles , Humanos , Técnicas Biosensibles/métodos , Metiltransferasas/genética , Metilación de ADN , ADN/genética , Técnicas ElectroquímicasRESUMEN
Green-emissive carbon nanodots (CDs) with high quantum yield are prepared. The abundant functional groups on the surfaces of CDs can selectively interact with Cu2+. The formed cupric amine complexes induce significant fluorescence quenching. The "on-off" switching can be further adjusted to the fluorescence "on" mode by the introduction of glutathione (GSH), which hinders the interactions between CDs and Cu2+. Based on the fantastic optical behavior of CDs, highly sensitive detection of Cu2+ and GSH can be achieved. Intracellular imaging of the two targets is also validated.
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Carbono , Glutatión , Espectrometría de Fluorescencia/métodosRESUMEN
Early quantification of multiplex biomarkers such as microRNAs (miRNAs) is critical during disease pathologic development and therapy. To tackle challenges of low abundance and multiplexing, we herein report a mass-encoded biosensing approach with duplex-specific nuclease (DSN) mediated signal amplification. Magnetic Fe3O4 cores are coated with small gold nanoparticles (AuNPs), which are applied to achieve facile DNA immobilization subsequent separation. This biosensor integrates multiple mass reporters corresponding to different targets (five miRNAs as examples). Due to the excellent resolution of mass spectrometry, these targets can be successfully distinguished in a single spectrum. Wide detection ranges from 10 fM to 1 nM are achieved, and the limits of detection are estimated to be 10 fM. High selectivity is promised due to the enzyme activity of DSN, and practical application in human serum samples performs satisfactorily. The number of targets to be tested can be further expanded by designing different specific mass tags in theory. Therefore, the proposed method can be utilized as an important and valuable tool to quantify multiplex miRNAs for disease screening as well as biomedical investigations.
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Espectrometría de Masas , Técnicas de Amplificación de Ácido Nucleico , MicroARNs/química , Espectrometría de Masas/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Ribonucleasas/metabolismo , Técnicas Biosensibles/métodos , Oro , Nanopartículas del MetalRESUMEN
The concentration of circulating tumor cells (CTCs) in peripheral blood is strongly correlated with the progress of certain metastatic cancers. In this study, we have developed a novel and facile electrochemical biosensor for the detection of CTCs based on the use of manganese dioxide nanosheets (MnO2 NSs) and gold nanoparticles (AuNPs). Aptamer sequence of target cell is modified on the surface of AuNPs for specifical recognition. With low-speed centrifugation, numerous AuNPs@DNA can be removed from the supernatant. On the other hand, MnO2 NSs are modified on the electrode surface to capture unreacted AuNPs@DNA. The declined electrochemical signal intensity can be used to reflect the level of CTCs. This biosensor achieves a wide linear range from 10 to 104 cells mL-1 and a limit of detection as low as 3 cells mL-1. Due to the specific aptamer as the recognition element, interfering cells can be successfully distinguished and this method performs satisfactorily in clinical samples. Therefore, it has great potential to be used as a powerful tool benefiting rare cells analysis and the investigation of dynamics of cellular interactions.
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Técnicas Biosensibles , Oro , Compuestos de Manganeso , Nanopartículas del Metal , Células Neoplásicas Circulantes , Óxidos , Humanos , Técnicas Electroquímicas , Comunicación CelularRESUMEN
Objective: For elderly patients aged ≥75 with esophageal cancer, whether surgical treatment is safe and effective and whether it is feasible to use a relatively radical "no tube, no fasting" fast-track recovery protocol remain topics of debate. We conducted a retrospective analysis to shed light on these two questions. Methods: We retrospectively collected the data of patients who underwent McKeown minimally invasive esophagectomy (MIE) combined with early oral feeding (EOF) on postoperative day 1 between April 2015 and December 2017 at Medical Group 1, Ward 1, Department of Thoracic Surgery of our hospital. Preoperative characteristics, postoperative complications, operation time, intraoperative blood loss, duration of anastomotic leakage (day), hospital stay, and survival were evaluated. Results: Twenty-three elderly patients with esophageal cancer underwent surgery with EOF. No significant difference was observed in intraoperative measures. The incidence of postoperative complications was 34.8% (8/23). Two patients (8.7%) were terminated early during the analysis of the feasibility of EOF. For all 23 patients, the mean hospital stay was 11.4 (5-42) days, and the median survival was 51 months. Conclusion: Patients aged ≥75 with resectable esophageal cancer can achieve long-term survival with active surgical treatment. Moreover, the "no tube, no fasting" fast-track recovery protocol is safe and feasible for elderly patients.
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Objective: To investigate the feasibility of multimodal regimen by paracetamol, gabapentin, ketamine, lidocaine, dexmedetomidine and sufentanil among cardiac surgery patients, and compare the analgesia efficacy with conventional sufentanil-based regimen. Design: A single-center, prospective, randomized, controlled clinical trial. Setting: One participating center, the cardiovascular center of the major integrated teaching hospital. Participants: A total of 115 patients were assessed for eligibility: 108 patients were randomized, 7 cases were excluded. Interventions: The control group (group T) received conventional anesthesia management. Interventions in the multimodal group (group M) were as follows in addition to the standard of care: gabapentin and acetaminophen 1 hour before surgery; ketamine for induction and to maintain anesthesia with lidocaine and dexmedetomide. Ketamine, lidocaine, and dexmedetomidine were added to routine sedatives postoperatively in group M. Measurements and Main Results: The incidence of moderate-to-severe pain on coughing made no significant difference (68.5% vs 64.8%, P=0.683). Group M had significantly less sufentanil use (135.72µg vs 94.85µg, P=0.000) and lower rescue analgesia rate (31.5% vs 57.4%, P=0.007). There was no significant difference in the incidence of chronic pain, PONV, dizziness, inflammation index, mechanical ventilation time, length of stay, and complications between the two groups. Conclusion: Our multimodal regimen in cardiac surgery is feasible, but was not superior to traditional sufentanil-based regimen in the aspects of analgesia effects; however, it did reduce perioperative opioid consumption along with rescue analgesia rate. Moreover, it showed the same length of stay and the incidences of postoperative complications.