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1.
Opt Express ; 29(23): 38615-38622, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808911

RESUMO

This paper proposes a binocular holographic floating display. The device consists of two phase-modulation spatial light modulators (SLM) and a dihedral corner reflector array (DCRA) element. The conjugate images of the SLMs generated by the DCRA become the system's exit pupils. Exit pupils that are larger than the pupils of human eyes are arranged to locate at the position of observer's eyes. Therefore, the dimension of the SLM will not limit the viewing angle, although the pixel pitch of the SLM still limits the maximum field of view. For the laser light source, the resolution of the images can achieve 3 arc minutes when the distance between images and DCRA is less than 20 cm. The full-color display function is also performed in the proposed device.

2.
Opt Express ; 29(21): 33679-33693, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809175

RESUMO

This study presents a partially coherent illumination based (PCI-based) SIM apparatus for dual-modality (phase and fluorescent) microscopic imaging. The partially coherent illumination (PCI) is generated by placing a rotating diffuser on a monochromatic laser beam, which suppresses speckle noise in the dual-modality images and endows the apparatus with sound sectioning capability. With this system, label-free quantitative phase and super-resolved/sectioned fluorescent images can be obtained for the same sample. We have demonstrated the superiority of the system in phase imaging of transparent cells with high endogenous contrast and in a quantitative manner. In the meantime, we have also demonstrated fluorescent imaging of fluorescent beads, rat tail crosscut, wheat anther, and hibiscus pollen with super-resolution and optical sectioning. We envisage that the proposed method can be applied to many fields, including but not limited to biomedical, industrial, chemistry fields.

3.
J Hazard Mater ; : 127689, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34799173

RESUMO

Monoclonal antibodies (mAbs) are useful biological tools for research, diagnostics, and pharmaceuticals. Here, we proposed a new mAb discovery platform named the two-step cell selection method (TCSM) for mAbs production of some small molecule haptens as antibiotic, toxins, and pesticides. The first step was performed by a fluorescence-activated cell sorter to enrich the hapten-specific B cells, the second step was an image-based precise pick of single hapten-specific hybridoma cells by confocal laser scanning microscopy. In this study, we used tetramethylenedisulfotetramine (TETS) as a model analyte, which is a highly lethal neurotoxic rodenticide. The TETS-specific hybridoma cells selection was completed within 10 days by the TCSM, compared with at least 40 days in the traditional hybridoma method (THM). The half maximal inhibitory concentration (IC50) of the best mAb 1G6 for TETS in the TCSM was 1.98 ng mL-1, and that of mAb 2B6 in the THM was 11.49 ng mL-1. Antibody-TETS recognition also showed more interactions in mAb 1G6 than in mAb 2B6. Then, the mAb 1G6 was then successfully applied to develop an icELISA for TETS in biological samples with satisfactory sensitivity, accuracy and precision. The results demonstrated that the TCSM was a feasible and efficient method for mAb discovering of poisonous hapten molecules.

4.
Postgrad Med ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762815

RESUMO

INTRODUCTION AND OBJECTIVES: Artificial intelligence (AI) made it achievable that aortic dilation could be measured in CT images indirectly, while aortic diameter (AD) has the certain relationship with blood pressure. It was potential that the blood pressure condition be determined by AD measurement using the data obtained from a CT scanning especially in identifying masked hypertension and predicting the risk of poor control of blood pressure (BP) which was easy to elude diagnosis in clinic. We aimed to evaluate the possibility of utilizing AD by AI for predicting the risk of adverse BP status (including masked hypertension or poor BP control) and the optimal thoracic aortic position in measurement as well as the cut-off value for predicting the risk. METHODS: 801 patients were enrolled in our study. AI-Rad Companion Cardiovascular (K183268 FDA approved) was used to perform automatic aorta measurement in thoracic CT images at 9 key positions based on AHA guidelines. Data was post processed by software from AI-Rad Companion undergone rigorous clinical validation by both FDA and CE as verification of its efficacy and usability. The AD's risk and diagnostic value were assessed in identifying hypertension in the general population, in identifying the poor BP controlled in the hypertension population, and in screening masked hypertension in the general population respectively by multiple regression analysis and receiver operating curve analysis. RESULTS: AD measured by AI was a risk factor for adverse BP status after clinical covariates adjustment (OR=1.02~1.26). The AD at mid descending aorta was mostly affected by BP particularly, which is optimal indicator in identifying hypertension in the general population (AUC=0.73) and for screening masked hypertension (AUC=0.78). CONCLUSION: Using AI to measure the AD of the aorta, particularly at the position of mid descending aorta, is greatly valuable for identifying people with poor BP status. It will be possible to reveal more clinical information reflected by ordinary CT images and enrich the screening methods for hypertension, especially masked hypertension.

5.
J Mater Chem B ; 9(37): 7597-7607, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34596205

RESUMO

Enzyme immobilization has been accepted as a powerful technique to solve the drawbacks of free enzymes such as limited activity, stability and recyclability under harsh conditions. Different from the conventional immobilization methods, enzyme immobilization in inorganic hybrid nanoflowers was executed in a biomimetic mineralization manner with the advantages of mild reaction conditions, and thus it was beneficial to obtain ideal biocatalysts with superior characteristics. The key factors influencing the formation of enzyme-based inorganic hybrid nanoflowers were elucidated to obtain a deeper insight into the mechanism for achieving unique morphology and improved properties of immobilized enzymes. To date, immobilized enzymes in inorganic hybrid nanoflowers have been successfully applied in biocatalysis for preparing medical intermediates, biodiesel and biomedical polymers, and solving the environmental or food industrial issues such as the degradation of toxic dyes, pollutants and allergenic proteins. Moreover, they could be used in the development of various biosensors, which provide a promising platform to detect toxic substances in the environment or biomarkers associated with various diseases. We hope that this review will promote the fundamental research and wide applications of immobilized enzymes in inorganic hybrid nanoflowers for expanding biocatalysis and biosensing.

6.
ACS Omega ; 6(41): 27101-27111, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34693130

RESUMO

X-ray photoelectron and near-edge X-ray absorption fine structure (NEXAFS) spectra, as well as the ground-state electronic/geometrical structures of a newly discovered nonclassical isomer C 2v -C66(NC), and two classical fullerene isomers C 2-#4466C66 and C s -#4169C66 with their hydrogenated derivatives [C 2v -C66H4(NC), C 2-#4466C66H4, and C s -#4169C66H4] have been calculated at the density functional theory (DFT) level. Significant differences were observed in the electronic structures and simulated X-ray spectra after hydrogenation. Simultaneously, both X-ray photoelectron and NEXAFS spectra reflected conspicuous isomer dependence, indicating that the "fingerprints" in the X-ray spectra can offer an effective method for identifying the above-mentioned fullerene isomers. The simulated ultraviolet-visible (UV-vis) absorption spectroscopy of C 2v -C66H4(NC) has also been generated by means of the time-dependent DFT method, and the calculations are well consistent with the experimental results. Consequently, this work reveals that X-ray and UV-vis spectroscopy techniques can provide valuable information to help researchers explore the fullerene electronic structure and isomer identification on the future experimental and theoretical fullerene domains.

7.
ACS Omega ; 6(41): 27259-27270, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34693146

RESUMO

The adsorption behaviors of CO2 at the Cu n /TiC(001) interfaces (n = 1-8) have been investigated using the density functional theory method. Our results reveal that the introduction of copper clusters on a TiC surface can significantly improve the thermodynamic stability of CO2 chemisorption. However, the most stable adsorption site is sensitive to the size and morphology of Cu n particles. The interfacial configuration is the most stable structure for copper clusters with small (n ≤ 2) and large (n ≥ 8) sizes, in which both Cu particles and TiC support are involved in CO2 activation. In such a case, the synergistic behavior is associated with the ligand effect introduced by directly forming adsorption bonds with CO2. For those Cu n clusters with a medium size (n = 3-7), the configuration where CO2 adsorbs solely on the exposed hollow site constructed by Cu atoms at the interface shows the best stability, and the charger transfer becomes the primary origin of the synergistic effect in promoting CO2 activation. Since the most obvious deformation of CO2 is observed for the TiC(001)-surface-supported Cu4 and Cu7 particles, copper clusters with specific sizes of n = 4 and 7 exhibit the best ability for CO2 activation. Furthermore, the kinetic barriers for CO2 dissociation on Cu4- and Cu7-supported TiC surfaces are determined. The findings obtained in this work provide useful insights into optimizing the Cu/TiC interface with high catalytic activation of CO2 by precisely controlling the size and dispersion of copper particles.

9.
J Food Sci ; 86(10): 4754-4767, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34549423

RESUMO

Fluorescence polarization immunoassay (FPIA) is a homogeneous and rapid analytical method that is suitable for high-throughput screening of large numbers of samples. However, FPIA typically suffers from lower sensitivity than the well-established enzyme-linked immunosorbent assay (ELISA), limiting its wide application as an analytical tool that can be run with trace levels of an analyte. Herein, a highly sensitive FPIA for detecting amantadine (AMD) in chicken is described. To achieve high sensitivity, nine chemical tracers of AMD that employ different fluoresceins, fluorescein derivatives, and haptens were synthesized and paired with four previously produced monoclonal antibodies (mAbs). The effect of the tracer structure on the sensitivity of FPIA was investigated and discussed. We found that the tracers with a linear and shorter bridge between adamantane and fluorescein generally provided higher sensitivity. After optimization, N'-(1-adamantyl) ethylenediamine (AEDA), an AMD structural analogue labeled with fluorescein isothiocyanate (FITC), achieved the lowest IC50 value (1.0 ng/ml) in the FPIA, which was comparable to that of the heterologous ELISA format that used the same mAb7G2. We also investigated the possible recognition mechanism of mAbs in terms of conformational and electronic aspects. The developed FPIA was applied to chicken to detect AMD residue, demonstrating a limit of detection (LOD) of 0.9 µg/kg with recoveries of 76.5-89.3% and coefficients of variation (CVs) below 14.5%. These results show that the proposed FPIA is an efficient, accurate, and convenient method for the rapid screening of AMD residues in chicken. PRACTICAL APPLICATION: The fluorescence polarization immunoassay (FPIA) was developed to determine and quantify amantadine (AMD) in chicken samples with high sensitivity. This homogeneous method avoids coating and washing steps and may provide high-throughput AMD screening in chicken in 10 min with high accuracy and precision. FPIA can be used as a monitoring tool and contribute significantly to the rapid detection of AMD in chicken.


Assuntos
Amantadina , Imunoensaio de Fluorescência por Polarização , Análise de Alimentos , Carne , Amantadina/análise , Animais , Galinhas , Ensaio de Imunoadsorção Enzimática , Análise de Alimentos/métodos , Limite de Detecção , Carne/análise
10.
Anal Chem ; 93(37): 12514-12523, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34490773

RESUMO

Despite that the currently discovered CRISPR-Cas12a system is beneficial for improving the detection accuracy and design flexibility of luminescent biosensors, there are still challenges to extend target species and strengthen adaptability in complicated biological media. To conquer these obstacles, we present here some useful strategies. For the former, the limitation to nucleic acids assay is broken through by introducing a simple functional DNA regulation pathway to activate the unique trans-cleavage effect of this CRISPR system, under which the expected biosensors are capable of effectively transducing a protein (employing dual aptamers) and a metal ion (employing DNAzyme). For the latter, a time-gated luminescence resonance energy transfer imaging manner using a long-persistent nanophosphor as the energy donor is performed to completely eliminate the background interference and a nature-inspired biomimetic periodic chip constructed by photonic crystals is further combined to enhance the persistent luminescence. In line with the above efforts, the improved CRISPR-Cas12a luminescent biosensor not only exhibits a sound analysis performance toward the model targets (carcinoembryonic antigen and Na+) but also owns a strong anti-interference feature to actualize accurate sensing in human plasma samples, offering a new and applicative analytical tool for laboratory medicine.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Biomimética , Sistemas CRISPR-Cas/genética , DNA/genética , Humanos , Luminescência
11.
J Hepatocell Carcinoma ; 8: 985-996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466409

RESUMO

Ferroptosis is a special form of regulatory cell death caused by the accumulation of intracellular iron and lipid peroxidation. Here, we summarize the research progress on ferroptosis in hepatocellular carcinoma (HCC), trace the development of the concept of ferroptosis and its key regulatory factors, and discuss the application value of ferroptosis in the treatment of HCC from different perspectives. We believe that exploring the relationship between ferroptosis and HCC and clarifying the metabolism and expression of ferroptosis-specific genes and molecules will accelerate the development of novel ferroptosis-related molecules as HCC markers and therapeutic targets. We hope to provide a theoretical basis for better diagnosis and treatment to effectively improve the prognosis of patients with HCC.

12.
JACS Au ; 1(8): 1178-1186, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34467356

RESUMO

Two-dimensional (2D) perovskites are emerging as promising candidates for diverse optoelectronic applications because of low cost and excellent stability. In this work, we explore the electronic structures and interfacial properties of (4Tm)2PbI4 with both the collinear and noncollinear DFT (PBE and HSE06) methods. The results evidently manifest that explicitly considering the spin-orbit coupling (SOC) effects is necessary to attain correct band alignment of (4Tm)2PbI4 that agrees with recent experiments (Nat. Chem.2019, 11, 1151; Nature2020, 580, 614). The subsequent time-domain noncollinear DFT-based nonadiabatic carrier dynamics simulations with the SOC effects reveal that the photoinduced electron and hole transfer processes are asymmetric and associated with different rates. The differences are mainly ascribed to considerably different nonadiabatic couplings in charge of the electron and hole transfer processes. Shortly, our current work sheds important light on the mechanism of the interfacial charge carrier transfer processes of (4Tm)2PbI4. The importance of the SOC effects on correctly aligning the band states of (4Tm)2PbI4 may be generalized to similar organic-inorganic hybrid 2D perovskites having heavy Pb atoms.

13.
ISA Trans ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34493382

RESUMO

This paper proposes a digital twin solution for unsteady flow state estimation in a pumping station. Digital twin is expected to accurately estimate the real-time hydraulic parameters of blind spots of the pumping station system even under some adverse conditions including the interference of observation noise and model parameters drift. To solve these challenges, a digital twin framework integrating the model-driven method, control theory and data-driven method is presented. In this framework, an unsteady flow state estimation method combining frequency domain analysis and generalized predictive control theory is developed for the first time, which is superior to traditional time-domain numerical discrete methods in terms of computational efficiency and anti-noise interference. In the model parameter calibration process, the novelty concerns modeling of the optimization problem considering the dynamic operation control of the station and unsteady flow of pipelines. And this process is accomplished through the comprehensive application of the model-free adaptive control algorithm, the transient flow model and the particle swarm optimization algorithm. This work is applied to a pumping station in a product pipeline to verify its effectiveness in estimating the transient flow state of data blind spots and map the dynamic operation behavior under the interference of colored noise and parameter drift.

14.
Molecules ; 26(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34577037

RESUMO

Theoretically, sandwich immunoassay is more sensitive and has a wider working range than that of competitive format. However, it has been thought that small molecules cannot be detected by the sandwich format due to their limited size. In the present study, we proposed a novel strategy for achieving sandwich immunoassay of ß-lactams with low molecular weights. Firstly, five ß-lactam antibiotics were selected to bind with penicillin binding protein (PBP)2x* to form complexes. Then, monoclonal and polyclonal antibodies against PBP2x*-ß-lactams complexes were produced by animal immunization. Subsequently, the optimal pairing antibodies were utilized to establish sandwich immunoassay for detection of 18 PBP2x*-ß-lactam complexes. Among them, ceftriaxone could be detected at as low as 1.65 ng/mL with working range of 1-1000 ng/mL in milk. To reveal the detection mechanism, computational chemistry and molecular recognition study were carried out. The results showed that ß-lactams with a large size and complex structures maybe conducive to induce conformational changes of PBP2x*, and then exhibit greater possibility of being detected by sandwich immunoassay after combination with PBP2x*. This study provides insights for subsequent investigations of anti-metatype antibody screening and sandwich immunoassay establishment for small-molecule detection.


Assuntos
Proteínas de Ligação às Penicilinas , Streptococcus pneumoniae , beta-Lactamas , Antibacterianos , Testes de Sensibilidade Microbiana
15.
Blood Adv ; 5(21): 4465-4475, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34521106

RESUMO

Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated from 2017 through 2020 with axicabtagene ciloleucel (axi-cel; n = 89) or a bispecific CD19/CD22 CAR (n = 38). Twelve (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within the first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8 and 30 (median, 17.5) and thrombosis between days 2 and 91 (median, 29). Bleeding sites included genitourinary, soft tissue, intracranial, gastrointestinal, and pulmonary and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older, had lower baseline platelets (86 × 103/µL vs 178 × 103/µL; P < .01), lower platelet and fibrinogen nadirs , and elevated lactate dehydrogenase. Immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) grade ≥3 was associated with increased bleeding (50% vs 15%; P = .01), thrombosis (50% vs 16%; P = .04), prothrombin time prolongation, hypofibrinogenemia, and elevated D-dimer. Low pretreatment platelet counts were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding and should be closely monitored, particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR T therapy, including their association with neurotoxicity.

16.
AAPS PharmSciTech ; 22(6): 211, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34374899

RESUMO

This study evaluates the potential use of near-infrared hyperspectral imaging (NIR-HSI) for quantitative determination of the drug amount in inkjet-printed dosage forms. We chose metformin hydrochloride as a model active pharmaceutical ingredient (API) and printed it onto gelatin films using a piezoelectric inkjet printing system. An industry-ready NIR-HSI sensor combined with a motorized movable linear stage was applied for spectral acquisition. Initial API-substrate screening revealed best printing results for gelatin films with TiO2 filling. For calibration of the NIR-HSI system, escalating drug doses were printed on the substrate. After spectral pre-treatments, including standard normal variate (SNV) and Savitzky-Golay filtering for noise reduction and enhancement of spectral features, principal component analysis (PCA) and partial least squares (PLS) regression were applied to create predictive models for the quantification of independent printed metformin hydrochloride samples. It could be shown that the concentration distribution maps provided by the developed HSI models were capable of clustering and predicting the drug dose in the formulations. HSI model prediction showed significant better correlation to the reference (HPLC) compared to on-board monitoring of dispensed volume of the printer. Overall, the results emphasize the capability of NIR-HSI as a fast and non-destructive method for the quantification and quality control of the deposited API in drug-printing applications.


Assuntos
Imageamento Hiperespectral , Espectroscopia de Luz Próxima ao Infravermelho , Composição de Medicamentos , Análise dos Mínimos Quadrados , Controle de Qualidade
18.
Anal Chem ; 93(36): 12447-12455, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34449219

RESUMO

Alzheimer's disease (AD), known as a progressive neurodegenerative disorder, has had a terrible impact on the health of aged people. Due to its severity, early diagnosis of AD is significant to retard the progress and provide timely treatment. Here, we report a fluorescence ratio detection of AD biomarker amyloid ß oligomers (AßOs) by combining highly doped upconversion nanoparticles-SiO2@metal-organic framework/black hole quencher (H-USM/BHQ-1) microspheres with optical tweezer (OT) microscopic imaging. Optical trapping a single microsphere not only avoids the interference of fluid viscosity but also provides a high power density laser source to efficiently stimulate upconversion luminescence (UCL) of highly doped upconversion nanoparticles (H-UCNPs). Under this condition, H-UCNPs show stronger UCL and greater power-dependent properties compared to low-doped ones. Moreover, the closely packed quenching molecules BHQ-1 on a metal-organic framework (ZIF-8) exhibit excellent quenching efficiency for upconversion 525 and 540 nm emission. Also, the luminescent resonance energy transfer efficiency reaches 89.58%. When different concentrations of AßOs are present, the UCL540 recovers due to the decomposition of ZIF-8 and the release of BHQ-1. Using 540 and 654 nm emission ratio of highly doped UCNPs as reporters, the limit of detection reaches 28.4 pM for the quantitative determination of AßOs. Besides, this strategy is able to selectively quantify the AßO concentration. Therefore, we demonstrated the combination of optical trapping and highly doped UCNPs which is applied for the detection of AßOs with high sensitivity and specificity.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Idoso , Peptídeos beta-Amiloides , Humanos , Microesferas , Dióxido de Silício
19.
Blood Adv ; 5(16): 3147-3151, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34424318

RESUMO

Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Medula Óssea , Exame de Medula Óssea , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Prospectivos
20.
Liver Cancer ; 10(4): 320-329, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34414120

RESUMO

Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4-8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8-15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

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